JOURNAL HOME CME HOME THIS MONTH PAST ISSUES ETOC COLLECTIONS
AUTHORS REVIEWERS EDITORIAL BOARD FEEDBACK RSS HELP
A&A International Anesthesia Research Society
QUICK SEARCH:   [advanced]


     

This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a colleague
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via ISI Web of Science (4)
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Wang, S. Y.
Right arrow Articles by Segal, S.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Wang, S. Y.
Right arrow Articles by Segal, S.
Anesth Analg 2002;94:1304-1309
© 2002 International Anesthesia Research Society

OBSTETRIC ANESTHESIA

Pregnancy Alters Adrenergic Mechanisms in Uterine Arterioles of Rats

Steven Y. Wang, MD PhD, Sanjay Datta, MD, and Scott Segal, MD

Department of Anesthesiology, Perioperative, and Pain Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts

Address correspondence and reprint requests to Steven Y. Wang, MD, PhD, c/o Scott Segal, MD, Department of Anesthesiology, Perioperative, and Pain Medicine, Brigham and Women’s Hospital, 75 Francis St., Boston, MA 02115. Address e-mail to swang{at}communitymedical.org


   Abstract
Top
 Abstract
Introduction
 Methods
 Results
 Discussion
 References
 
Pregnancy is associated with altered vascular reactivity. However, the effect of pregnancy on the {alpha}- and ß-adrenergic responses in the uterine microcirculation remains to be determined. In late-pregnant (Day 20–21, n = 6) and virgin (n = 6) Sprague-Dawley rats, uterine radial arterioles (70–120 µm in internal diameter) were isolated. We studied in vitro arteriolar responses in a pressurized, no-flow state with videomicroscopy. {alpha}2-Adrenergic activation relaxed uterine arterioles; this relaxation was increased with pregnancy and was inhibited after endothelial denudation or inhibition of nitric oxide synthase. Pregnancy significantly increased the contractile response to the {alpha}1-adrenoceptor agonist phenylephrine but decreased the relaxation to the ß-adrenoceptor agonist isoproterenol. The contractile response to the protein kinase C activator phorbol ester and relaxation responses to both the adenylate cyclase activator forskolin and the endothelium-independent cyclic guanosine monophosphate-mediated vaso- dilator nitroprusside were preserved. These results suggest that pregnancy enhances the {alpha}2-adrenoceptor-mediated relaxation of uterine arterioles, probably because of an increase in the release of nitric oxide. The {alpha}1-adrenergic response is upregulated, whereas the ß-adrenergic response is impaired, in the uterine microcirculation of pregnant rats.

IMPLICATIONS: Both {alpha}- and ß-adrenergic responses are important mechanisms for the regulation of uteroplacental perfusion. By use of an in vitromicrovascular technique, we have shown pregnancy-associated alteration in adrenergic responses in the uterine microcirculation of the rat.


   Introduction
Top
 Abstract
 Introduction
Methods
 Results
 Discussion
 References
 
Pregnancy is associated with altered vascular reactivity. This may be because of an enhanced endothelium-dependent relaxation, intrinsic changes in the vascular smooth muscle, or alterations in the vascular adrenergic response. Both {alpha}- and ß-adrenergic regulations are important mechanisms in the control of uterine blood flow and fetal oxygenation. Previous studies have demonstrated that pregnancy increases the {alpha}1-adrenoceptor-mediated contraction of uterine arterioles in rats (1). Whereas {alpha}2-adrenergic stimulation induces an endothelium-dependent relaxation, it may cause a direct contraction in the vascular smooth muscle of pulmonary and systemic vessels (2). Activation of ß-adrenoceptors results in a cyclic adenosine monophosphate-mediated relaxation of various vascular beds. Previous studies have suggested that the ß-adrenergic response might be altered during pregnancy, as evidenced by downregulation of ß-adrenoceptors in the rat myometrium (3) and human lymphocytes (4) in pregnancy. In addition, in vivo cardiovascular responses to ß-adrenergic agonists are blunted in pregnant women (5). However, no previous investigation has examined the {alpha}2- and ß-adrenergic responses in the uterine arteriole, an important site for the regulation of uterine blood flow.

We hypothesized that pregnancy might result in increases in the {alpha}-adrenergic response and a decrease in the ß-adrenergic relaxation in the uterine microcirculation. In vitro arteriolar responses were studied with a video microscope in a no-flow state so that observations would not be influenced by neurohumoral and metabolic changes associated with an in vivo study. To evaluate the activity of the ß-adrenoceptor and adenylate cyclase, relaxation responses to isoproterenol and forskolin, respectively, were examined. To study {alpha}2-adrenergic responses, the guanosine 3', 5'-cyclic monophosphate-mediated and endothelium-dependent relaxation to the {alpha}2-adrenoceptor agonist clonidine was determined. In addition, the contractile response to the {alpha}1-adrenoceptor agonist phenylephrine and the protein kinase C (PKC) activator 12-deoxyphorbol 13-isobutyrate 20-acetate (phorbol ester) were also examined.


   Methods
Top
 Abstract
 Introduction
 Methods
Results
 Discussion
 References
 
The study protocol was approved by the Harvard Medical Area Standing Committee on Animals. Experiments were performed on female Sprague-Dawley rats. Pregnant rats (n = 6) were studied at 20–21 days’ gestation (term, 22 days). Age- and weight-matched virgin rats (n = 6) were used as controls. Animals were killed with an intraperitoneal injection of pentobarbital sodium (30 mg/kg). The entire uterus was rapidly excised, and fetuses and placentas were removed. The tissue was immediately placed in cold Krebs-Henseleit buffer solution (composition, in mM: Na+ 143, K+ 5.9, Ca2+ 2.6, Mg2+ 1.2, Cl- 128, H2PO4- 2.2, HCO3- 24.9, SO42- 1.2). Uterine radial arterioles were dissected with a 10–60x power dissecting microscope. Microvascular studies were performed as previously described in detail (6–8). Briefly, arterioles (70–120 µm in internal diameter and 0.5–1.0 mm in length) were placed into a Plexiglas organ chamber, cannulated with dual glass micropipettes measuring 30–80 µm in diameter, and secured with 10-O nylon monofilament sutures. Oxygenated (95% oxygen and 5% CO2) Krebs-Henseleit buffer solution warmed to 37°C (pH 7.4) was continuously circulated through an organ chamber and a reservoir containing a total volume of 100 mL. The arterioles were pressurized to 50 mm Hg in a no-flow state by using a burette manometer filled with Krebs-Henseleit buffer solution. With an inverted microscope (40–200x; Living System Instrumentation, Burlington, VT) connected to a video camera, the vascular image was projected onto a television monitor. A video-electronic dimension analyzer was used to measure internal diameter, and a pressure transducer was used to measure distending pressure. Vessels were allowed to bathe in the organ chamber for 30 min before intervention.

Three arterioles were examined from each pregnant rat. Five to six arterioles were examined from each nonpregnant rat because additional studies were performed in the nonpregnant group. The dose response to the same drug was examined only once in each arteriole to avoid tachyphylaxis. Only one dose response was performed in each arteriole for phorbol ester, for phenylephrine, or in the presence of a specific antagonist. Up to three drugs (combination of clonidine, isoproterenol, and nitroprusside or combination of clonidine, forskolin, and nitroprusside) were applied to each arteriole. The order of drug administration was random. All drugs were applied extraluminally. The dose response was determined with stepwise increases in log drug concentration. The arteriole was not washed between successive concentrations. Measurements were made 2–3 min after the drug was administered, after the response had stabilized on the basis of inspection of a plot of vessel diameter versus time on a chart recorder connected to the dimension analyzer. Arterioles were washed three times at the end of each dose-response intervention with Krebs-Henseleit buffer solution and allowed to equilibrate for 15 min between interventions. We found that after washings the arteriolar diameter was returned close to the baseline, with a variation of less than ±4%. The diameter measured after washing was used as the baseline diameter of the subsequent dose-response intervention. Approximately 100 min was required to complete three dose-response interventions. Previous studies have shown that microvessels are stable over a similar period of time (6,7).

After equilibration, uterine arterioles from both pregnant and nonpregnant rats were precontracted with phenylephrine by 25%–30% of the resting baseline diameter. Phenylephrine was administered with stepwise increases in concentration until 25%–30% precontraction was obtained. Preliminary studies showed that phenylephrine induced a constant precontraction up to 2 h (n = 3 in each group).

After precontraction, relaxation responses to isoproterenol (10-12 to 10-5 M), forskolin (10-9 to 10-6 M), clonidine (10-9 to 10-4 M), and sodium nitroprusside (10-9 to 10-4 M) were studied. In nonprecontracted arterioles, contractile responses to phenylephrine (10-9 to 10-4 M) and phorbol ester (10-6 M) were examined. Only one concentration of phorbol ester was studied for each arteriole because of the difficulty in washing out this drug. Measurements for phorbol ester were made at 10 and 20 min because of a slow onset of contraction.

To examine the contribution of {alpha}2- and endothelium-dependent relaxation, the response to clonidine was determined after pretreatment of vessels with the {alpha}2-adrenoceptor antagonist yohimbine (10-5 M) and in vessels in which the endothelium had been denuded. The selective removal of endothelial cells was accomplished by advancing a human hair (approximately 60 µm in diameter) into the arteriolar lumen to abrade the luminal surface, followed by intraluminal injection of air bubbles (6). Arterioles denuded of the endothelium showed a normal response to sodium nitroprusside but failed to relax in response to adenosine 5'-diphosphate (10-5 M). In addition, the response to clonidine was examined in vessels pretreated with the nitric oxide synthase inhibitor NG-nitro-L-arginine (10-5 M) for 20 min. To determine ß- and {alpha}1-adrenergic responses, isoproterenol and phenylephrine were applied to vessels pretreated with the ß1-adrenocepor antagonist atenolol (10-5 M) and the {alpha}1-adrenoceptor antagonist prazosin (10-5 M), respectively, for 20 min.

Phenylephrine, isoproterenol, sodium nitroprusside, adenosine 5'-diphosphate, and NG-nitro-L-arginine were obtained from Sigma Chemicals (St. Louis, MO). Clonidine, forskolin, and yohimbine were obtained from Research Biochem, Inc. (Natik, MA). Phorbol ester was obtained from Cancer Research, Inc. (Chanhassen, MN). All drugs were dissolved in ultrapure distilled water, except for forskolin, which was dissolved in dimethyl sulfoxide. Vehicle alone (distilled water or dimethyl sulfoxide) had no effect on the vessels, neither constricting untreated vessels nor dilating precontracted vessels (data not shown).

Arteriolar responses were expressed as the percentage relaxation of the phenylephrine-induced contraction or the percentage contraction of the baseline diameter (mean ± SEM). Comparisons of arteriolar responses in the Pregnant and Nonpregnant group were performed with two-way analysis of variance for repeated measures. A P value of <0.05 was considered to be significant.


   Results
Top
 Abstract
 Introduction
 Methods
 Results
Discussion
 References
 
Uterine arterioles ranged from 70 to 120 µm in internal diameter, averaging 105 ± 18 µm and 98 ± 21 µm in the Nonpregnant and Pregnant group, respectively. To determine the relaxation response, arterioles were precontracted with phenylephrine by 22% ± 2% in the Nonpregnant and 23% ± 2% in the Pregnant group.

The {alpha}1-adrenoceptor agonist phenylephrine and the PKC activator phorbol ester induced significant contractile responses in uterine arterioles. The response to phenylephrine was significantly increased in Pregnant compared with Nonpregnant rats (P < 0.01, Fig. 1). The response to phorbol ester was similar in both groups (Fig. 2). The contractile response to phenylephrine was significantly inhibited after pretreatment of vessels with the {alpha}1-adrenoceptor antagonist prazosin (Fig. 1).



View larger version (23K):
[in this window]
[in a new window]
  		Figure 1. In vitro responses of nonprecontracted uterine arterioles to phenylephrine from pregnant (n = 6) and nonpregnant (n = 6) rats. The response was also examined in nonpregnant rats (n = 6) in the presence of the {alpha}1-adrenoceptor antagonist prazosin (10-5 M). Arterioles were pressurized to 50 mm Hg in a no-flow state (see text for details). Responses are expressed as percentage contraction of baseline diameter. *P < 0.01 versus nonpregnant rats.

 


View larger version (17K):
[in this window]
[in a new window]
  		Figure 2. In vitro responses of nonprecontracted uterine arterioles to phorbol ester (10-6 M) from pregnant (n = 6) and nonpregnant (n = 6) rats. Responses are expressed as percentage contraction of baseline diameter at two time points after addition of phorbol ester.

 
Clonidine caused a significant relaxation in uterine arterioles. The relaxation was increased in Pregnant rats (P < 0.01 versus Nonpregnant rats, Fig. 3) and was inhibited after pretreatment of vessels with the {alpha}2-adrenoceptor antagonist yohimbine, after the nitric oxide synthase inhibitor NG-nitro-L-arginine, or after endothelial denudation.



View larger version (29K):
[in this window]
[in a new window]
  		Figure 3. In vitro responses of precontracted uterine arterioles to clonidine from pregnant (n = 6) and nonpregnant (n = 6) rats. The response was also examined in nonpregnant rats (n = 6) in the presence of the nitric oxide synthase inhibitor NG-nitro-L-arginine (10-5 M) or the {alpha}2-adrenoceptor antagonist yohimbine (10-5 M) or after endothelial denudation. Responses are expressed as percentage relaxation of phenylephrine-induced contraction. *P < 0.01 versus nonpregnant rats.

 
The ß-adrenoceptor agonist isoproterenol and the adenylate cyclase activator forskolin induced significant relaxation in uterine arterioles. The relaxation response to isoproterenol was reduced in Pregnant rats (P < 0.05 versus Nonpregnant rats, Fig. 4) or after pretreatment of vessels with the ß1-adrenoceptor antagonist atenolol (Fig. 4). However, the response to forskolin was similar in both groups (Fig. 5). Sodium nitroprusside relaxed uterine arterioles in both Pregnant and Nonpregnant rats, and the responses were similar in both groups (Fig. 6).



View larger version (24K):
[in this window]
[in a new window]
  		Figure 4. In vitro responses of precontracted uterine arterioles to isoproterenol from pregnant (n = 6) and nonpregnant (n = 6) rats. The response was also examined in nonpregnant rats (n = 6) in the presence of the {alpha}1-adrenoceptor antagonist atenolol (10-5 M). Responses are expressed as percentage relaxation of phenylephrine-induced contraction. *P < 0.01 versus nonpregnant rats.

 


View larger version (17K):
[in this window]
[in a new window]
  		Figure 5. In vitro responses of precontracted uterine arterioles to forskolin from pregnant (n = 6) and nonpregnant (n = 6) rats. Responses are expressed as percentage relaxation of phenylephrine-induced contraction.

 


View larger version (20K):
[in this window]
[in a new window]
  		Figure 6. In vitro responses of precontracted uterine arterioles to sodium nitroprusside from pregnant (n = 6) and nonpregnant (n = 6) rats. Responses are expressed as percentage relaxation of phenylephrine-induced contraction.

 

   Discussion
Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
References
 
This study may provide an explanation of the effect of {alpha}2-adrenergic stimulation on the uterine microcirculation. {alpha}2-Adrenoceptors are present on both vascular smooth muscle and endothelial cells, although relative numbers and activities may vary considerably (2). The stimulation of {alpha}2-adrenoceptors on vascular smooth muscle is associated with contraction in most vascular beds, whereas the activation of endothelial {alpha}2-adrenoceptors relaxes vascular smooth muscle through the release of endothelium-derived nitric oxide. In this study, clonidine-induced {alpha}2-adrenergic stimulation caused a significant relaxation of uterine arterioles. The relaxation response to clonidine was markedly reduced after mechanical denudation of the endothelium, inhibition of nitric oxide synthase, or {alpha}2-adrenergic blockade. These results suggest that in the rat uterine arteriole, relaxation to {alpha}2-adrenergic stimulation predominates and is caused by endothelium-dependent and nitric oxide-mediated mechanisms.

We observed that the relaxation produced by {alpha}2-adrenergic stimulation was significantly enhanced during pregnancy compared with in Nonpregnant rats. It is unlikely that the increased relaxation after {alpha}2-adrenergic stimulation was caused by upregulation of {alpha}2-adrenoceptors, because it has been reported that pregnancy is associated with a decrease in {alpha}2-adrenoceptor density in porcine uterine arteries (9) as well as in human platelets (10). Furthermore, because the response to the direct nitric oxide donor nitroprusside remained unchanged, it is likely that the pregnancy-induced alteration in response to {alpha}2-adrenergic stimulation was not due to changes in the activity of guanylate cyclase or other distal elements in the signal transduction pathway. These results suggest that an increased release of nitric oxide may be responsible for augmentation of the {alpha}2-adrenoceptor-mediated and endothelium-dependent relaxation in rat uterine arterioles. Our findings are consistent with previous work demonstrating that pregnancy is associated with an increase in the release of endothelium-derived nitric oxide in conduit uterine arteries (11) and an increased expression of nitric oxide synthase in the uterine artery of pregnant ewes (12).

The effect of pregnancy on the ß-adrenergic response in the uterine microcirculation has not been previously evaluated. We observed a decreased ß-adrenergic response of rat uterine arterioles during pregnancy, consistent with previous work in human lymphocytes (4) and in human parturients (5). Although this study has not specifically addressed the potential mechanism underlying a diminished ß-adrenergic response in the uterine arteriole, it may be due to alterations in the ß-adrenoceptor or regulatory steps proximal to adenylate cyclase, because the relaxation induced by the adenylate cyclase activator forskolin was pre- served. Catecholamine-induced desensitization of the ß-adrenoceptor may be responsible, at least in part, for alterations in the signal transduction pathway of the uterine vascular ß-adrenergic system. Although plasma concentrations of catecholamines are not altered dur- ing pregnancy, agonist-induced desensitization of uterine vascular ß-adrenoceptors might occur by catecholamines of fetal origin, because catecholamine concentrations sharply increase in the amniotic fluid at term gestation (13).

In this study, isoproterenol induced a relaxation of uterine arterioles. Although the relative contribution of ß1- and ß2-adrenoceptor subtypes was not examined, the rat uterine arteriole might contain a mixture of both ß1- and ß2-adrenoceptors because the relaxation response was only partially inhibited after ß1-adrenergic blockade with atenolol. Such a heterogeneous distribution of ß-adrenoceptor subtypes has been demonstrated in a single vascular bed in other species (14,15).

We found that pregnancy markedly increased {alpha}1-adrenoceptor-mediated contraction in uterine arterioles. These results are in contrast to the fact that vasoconstrictive responses of the systemic circulation to {alpha}1-adrenergic stimulation are decreased during pregnancy in both animals and humans (16). Thus, pregnancy may be associated with regional differences in vascular {alpha}1-adrenergic responses. These changes in systemic and uterine vascular responses to {alpha}1-adrenergic stimulation are most likely caused by changes in the number of {alpha}1-adrenergic receptors. Previous studies have demonstrated both an increase in {alpha}1-adrenoceptor density of the uterine circulation and a decrease in receptor density in systemic vascular beds during pregnancy (1). In addition, we found that responses to the PKC activator phorbol ester (i.e., direct activation of the {alpha}1-adrenergic second messenger) were not different between Pregnant and Nonpregnant groups. Our findings are consistent with a previous study showing that the pregnancy-induced increase in the {alpha}1-adrenergic response of the rat uterine arteriole may be related to altered cycling rates of G protein (1).

It might be argued that differences in the {alpha}- and ß-adrenergic response observed in the Pregnant and Nonpregnant rats could be due to different levels of gonadal steroids, because the concentration of plasma gonadal steroids was not measured in this study. However, a previous observation showed that neither estrogen nor progesterone, when added to the sera of nonpregnant rats, inhibited the chronotropic response to the ß-adrenoceptor agonist isoproterenol (17). Furthermore, the myometrial ß-adrenergic response was not altered by gonadal steroids in either rabbits (18) or oophorectomized guinea pigs (19). Moreover, the response to {alpha}1-adrenergic agonists has been examined during the estrous cycle and was found to remain unchanged in the rat uterine artery (20) as well as in the pulmonary and systemic circulation of ewes (21).

The exogenous administration of synthetic catecholamines (e.g., ephedrine and phenylephrine) during epidural or spinal anesthesia in obstetric patients is frequently used to treat systemic hypotension and maintain effective uteroplacental perfusion. Ephedrine induces {alpha}1-, {alpha}2-, and ß-adrenergic stimulation, primarily by the release of norepinephrine from nerve endings. Thus, cardiovascular responses to ephedrine represent mixed effects of at least three different types of adrenoceptors. Myocardial ß-adrenergic stimulation increases arterial blood pressure by inotropic and chronotropic effects. Whereas the {alpha}1-adrenergic effect induces uterine vasoconstriction, our results show that {alpha}2- and ß-adrenergic stimulation is associated with uterine arteriolar dilation. In contrast, synthetic catecholamines with a pure {alpha}1-adrenergic affinity (e.g., phenylephrine) increase arterial blood pressure by {alpha}1-adrenoceptor-mediated vasoconstriction. Although the safe use of phenylephrine in parturients has been reported after epidural (16) and spinal (22) anesthesia, ephedrine may nonetheless have less of an adverse effect on uterine blood flow during obstetric anesthesia. This preferential preservation of uterine blood flow was demonstrated more than 30 years ago in pregnant sheep (23). More recent work suggests that ephedrine’s beneficial effect may be due to increased release of nitric oxide in uterine arteries of pregnant ewes (24). Our study adds to this understanding by demonstrating upregulation of {alpha}2-adrenergic pathways in the pregnant uterine microcirculation. Thus, ephedrine may be superior to pure {alpha}1-adrenergic agents in preservation of uterine blood flow when treating hypotension during regional anesthesia because of an increase in {alpha}2-adrenoceptor-mediated and nitric oxide-induced vasodilatation.

Limitations of this study include the in vitronature of the study, the route of the drug administration (extraluminal versus intraluminal), and potential differences in the vascular adrenergic response of the uterine microcirculation in various species. Therefore, caution should be exercised when extrapolating our findings to clinical practice. Future study should be focused on the direct measurement of uterine blood flow in intact animals or human parturients with noninvasive techniques (e.g., Doppler imaging) and on the adrenergic regulation of the microcirculation in human myometrium.

In conclusion, this study demonstrates that {alpha}2-adrenergic stimulation produces a predominant relaxation of the vascular smooth muscle in rat uterine arterioles. Pregnancy increases endothelium-dependent and {alpha}2-adrenoceptor-mediated relaxation through a release of endothelium-derived nitric oxide. The {alpha}1-adrenergic response is upregulated, whereas ß-adrenoceptor-mediated relaxation is impaired, in the uterine microcirculation of pregnant rats.


   Acknowledgments
 
We wish to thank Dr. G. Stahl for his technical assistance in the microvascular study.


   References
Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
 References
 

  1. D’Angelo G, Osol G, Cipolla M. Interaction of myogenic and adrenergic mechanisms in isolated, pressurized uterine radial arteries from late-pregnant and non-pregnant rats. Am J Obstet Gynecol 1993; 168: 697–705.[ISI][Medline]
  2. Vanhoutte PM, Miller VM. {alpha}2-Adrenoceptors and endothelium-derived relaxing factor. Am J Med 1989; 87 (Suppl 3C): 1S–5S.[Medline]
  3. Legrand C, Maltier JP, Benghan-Eyene Y. Rat myometrial adrenergic receptors in late pregnancy. Biol Reprod 1987; 37: 641–50.[Abstract]
  4. Nisell H, Martinsson A, Hjemdahl P. Reduced {alpha}2-adrenoceptor sensitivity in normal pregnancy but not in pregnancy-induced hypertension. Gynecol Obstet Invest 1988; 25: 262–7.[ISI][Medline]
  5. DeSimone CA, Leighton BL, Norris M, et al. The chronotropic effect of isoproterenol is reduced in term pregnant women. 1988;69:626–8.
  6. Wang SY, Friedman M, Franklin A, Sellke FW. Myogenic reactivity of coronary resistance arteries after cardiopulmonary bypass and hyperkalemic cardioplegia. Circulation 1995; 92: 1590–6.[Abstract/Free Full Text]
  7. Sellek FW, Myers PR, Bates JN, Harrison DG. Influence of vessel size on the sensitivity of porcine coronary microvessels to nitroglycerin. Am J Physiol 1990; 258: H515–20.[Abstract/Free Full Text]
  8. Cameron EM, Wang SY, Fink MP, Sellke FW. Mesenteric and skeletal muscle microvascular responsiveness in subacute sepsis. Shock 1998; 9: 184–92.[ISI][Medline]
  9. Guenther AE, Conley AJ, Van Orden DE, et al. Structural and mechanical changes in uterine arteries during pregnancy in the pig. J Anim Sci 1988; 66: 3144–52.
  10. Metz A, Stump K, Cowen PJ, et al. Changes in platelet ß2-adrenoceptor binding post partum: possible relation to maternity blues. Lancet 1983; 1: 495–8.[ISI][Medline]
  11. Ni Y, Meyer M, Osol G. Gestation increases nitric oxide-mediated vasodilation in rat uterine arteries. Am J Obstet Gynecol 1997; 176: 856–64.[ISI][Medline]
  12. Magness RR, Shaw CE, Phernetton TM, et al. Endothelial vasodilator production by uterine and systemic arteries. II. Pregnancy effects on NO synthase expression. Am J Physiol 1997; 272 (4 Pt 2):H1730–H1740.[Abstract/Free Full Text]
  13. Phillippe M. Fetal catecholamines. Am J Obstet Gynecol 1983; 146: 840–55.[ISI][Medline]
  14. Purdy RE, Stupecky GL, Coulombe PR. Further evidence for a homogeneous population of beta-1-adreceptors in bovine coronary artery. J Pharmacol Exp Ther 1988; 245: 67–71.[Abstract/Free Full Text]
  15. Wang SY, Friedman M, Johnson RG, et al. Adrenergic regulation of coronary microcirculation after extracorporeal circulation and crystalloid cardioplegia. Am J Physiol 1994; 267 (6 Pt 2):H2462–H2470.[Abstract/Free Full Text]
  16. McLaughlin MK, Keve TM, Cooke R. Vascular catecholamine sensitivity during pregnancy in the ewe. Am J Obstet Gynecol 1989; 160: 47–53.[ISI][Medline]
  17. Carli A, Auclair MC, Bleichner G, et al. Inhibitory action of human serum on the isoprenaline-induced chronotropic effect in cultured rat heart cells: influence of sex and pregnancy. Biomedicine 1977; 27: 166–8.[ISI][Medline]
  18. Riemer RK, Roberts JM. Endocrine modulation of myometrial response. In: Huszar G, ed. The physiology and biochemistry of the uterus in pregnancy and labor. Boca Raton, FL: CRC Press, 1986: 53–71.
  19. Hatjis CG, Grogan DM, Koritnik DR. Treatment of oophorectomized guinea pigs with intrauterine 17ß-adrenergic receptor binding properties. Am J Obstet Gynecol 1989; 161: 1628–32.[ISI][Medline]
  20. Osol G, Cipolla M. Interaction of myogenic and adrenergic mechanisms in isolated, pressurized uterine radial arteries from late-pregnant and non-pregnant rats. Am J Obstet Gynecol 1993; 168: 697–705.
  21. Shaul PW, Magness RR, Muntz KH, et al. {alpha}1-Adrenergic receptors in pulmonary and systemic vascular smooth muscle: alterations with development and pregnancy. Circ Res 1990; 67: 1193–200.[Abstract/Free Full Text]
  22. Ralston DH, Shnider SM, Delorimier AA. Effects of equipotent ephedrine, metaraminol, mephentermine, and methoxamine on uterine blood flow in the pregnant ewe. Anesthesiology 1974; 40: 354–70.[ISI][Medline]
  23. James FM III, Greiss FC Jr, Kemp RA. An evaluation of vasopressor therapy for maternal hypotension during spinal anesthesia. Anesthesiology 1970; 33: 25–34.[ISI][Medline]
  24. Li P, Tong C, Eisenach JC. Pregnancy and ephedrine increase the release of nitric oxide in ovine uterine arteries. Anesth Analg 1996; 82: 288–93.[Abstract]
Accepted for publication December 5, 2001.




This article has been cited by other articles:


Home page
 Anesth. Analg.Home page
S. Segal and S. Y. Wang
The Effect of Maternal Catecholamines on the Caliber of Gravid Uterine Microvessels
Anesth. Analg., March 1, 2008; 106(3): 888 - 892.
[Abstract] [Full Text] [PDF]

Home page
 J. Appl. Physiol.Home page
A. E. Nesbitt, R. J. Murphy, and K. P. O'Hagan
Effect of gestational stage on uterine artery blood flow during exercise in rabbits
J Appl Physiol, December 1, 2005; 99(6): 2159 - 2165.
[Abstract] [Full Text] [PDF]

This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a colleague
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via ISI Web of Science (4)
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Wang, S. Y.
Right arrow Articles by Segal, S.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Wang, S. Y.
Right arrow Articles by Segal, S.

Lippincott, Williams & Wilkins Anesthesia & Analgesia® is published for the International Anesthesia Research Society® by Lippincott Williams & Wilkins with the assistance of Stanford University Libraries' HighWire Press®. Copyright 2006 by the International Anesthesia Research Society. Online ISSN: 1526-7598   Print ISSN: 0003-2999 HighWire Press