Role of nitric oxide in the regulation of vascular tone in pressurized and perfused resistance myometrial arteries from term pregnant women

Kublickiene, Karolina; Cockell, Anna P.; Nisell, Henry; Poston, Lucilla

doi:10.1016/s0002-9378(97)70048-6

Cited by 70 publications

(69 citation statements)

References 17 publications

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“…Inhibition of PGHS pathway in the mouse vasculature did not contribute to the enhancement of myogenic tone in either nonpregnant or pregnant mice. Our finding is in agreement with a study on resistance myometrial arteries that showed absence of PGHS pathways on myogenic tone (22). These results overall indicate that endothelial-derived NO modulates myogenic tone in mesenteric and uterine arteries isolated from pregnant mice.…”

Section: Discussionsupporting

confidence: 93%

Vascular adaptations to pregnancy in mice: effects on myogenic tone

Veerareddy

Cooke

Baker

et al. 2002

American Journal of Physiology-Heart and Circulatory Physiology

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The mechanisms underlying vascular adaptations in pregnancy remain to be fully elucidated. One of the contributory mechanisms for reduced vascular tone may be a reduction of myogenic tone. Myogenic tone was assessed as the difference between internal diameter in the presence and absence of external calcium at different intramural pressure steps (60–100 mmHg). Myogenic responses were reduced in resistance-sized mesenteric and main uterine arteries in late pregnant compared with nonpregnant C57BL/6J mice. In vessels from pregnant, but not nonpregnant mice, the myogenic response was enhanced by preincubation with nitric oxide (NO) synthase inhibitor N G-nitro-l-arginine methyl ester, was further elevated by the gap junction inhibitor 18-α glycyrrhetinic acid, but was unaltered by the prostaglandin H synthase inhibitor meclofenamate. Endothelium removal enhanced myogenic tone only in the vessels from pregnant animals, thus confirming the role of the endothelium in modulating myogenic tone in pregnancy. These results suggest that endothelium-derived NO as well as gap junction communications modulate myogenic tone in mouse pregnancy.

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Section: Discussionsupporting

confidence: 93%

Vascular adaptations to pregnancy in mice: effects on myogenic tone

Veerareddy

Cooke

Baker

et al. 2002

American Journal of Physiology-Heart and Circulatory Physiology

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“…Other investigators reported that chronic increases in blood flow result in increased diameter, a process that normalizes shear stress (18,19,48). Furthermore, flow-mediated dilation is enhanced in small subcutaneous (4) and myometrial arteries (20) during human pregnancy and in the presence of N-nitro-L-arginine methyl ester (L-NAME), an inhibitor of NO; the response to increasing shear stress was similar to that of nonpregnant women. Interestingly, 17␤-estradiol stimulated flowmediated relaxation in small subcutaneous arteries from postmenopausal women but not premenopausal or pregnant women.…”

Section: Discussionmentioning

confidence: 94%

“…Of physiological and clinical importance, preeclamptic pregnancy is associated with reduced flow-mediated vasodilation (4) associated with a lower circulating estrogen level and attenuated release of NO. However, this response may be restored via exogenous estrogen treatment (15,20,21). Thus the increase in eNOS expression in the smaller diameter UA observed in midpregnant ewes, which is followed by a decreasing expression gradient in late gestation and a concomitant rise in NO x levels and an increase in diameter of UA 1°, may represent an adaptive mechanism that serves to normalize shear stress to physiological levels.…”

Section: Discussionmentioning

confidence: 99%

Endothelial vasodilator production by uterine and systemic arteries. IX. eNOS gradients in cycling and pregnant ewes

Joyce

Phernetton

Shaw

et al. 2002

American Journal of Physiology-Heart and Circulatory Physiology

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The follicular phase (FOL) and pregnancy exhibit increases in uterine blood flow (UBF), estrogen levels, and uterine artery (UA) endothelial nitric oxide synthase (eNOS) expression. UA branching within the mesometrium increases the total vascular cross-sectional area, which reduces the vascular perfusion pressure gradient, thus locally decreasing the blood flow velocity. Shear stress (SS) activates eNOS and may be associated with UBF elevations during FOL and pregnancy. We hypothesized that regional differences in eNOS responses are observed with both decreases in vessel diameter and during the ovarian cycle and pregnancy. Endothelial isolated proteins were collected from renal (RA) and internal iliac arteries (II) as well as from primary (UA 1°), secondary (UA 2°), and tertiary (UA 3°) UA branches of nonpregnant luteal phase (LUT; n ϭ 6) and FOL (n ϭ 6) as well as midpregnant (MP; 82 Ϯ 1 days gestation, n ϭ 6) and late pregnant (LP; 127 Ϯ 3 days gestation, n ϭ 6) ewes (term ϭ 145 Ϯ 3 days gestation) for Western blot analysis. LUT RA, II, and UA 1°eNOS levels were similar. There was a 60.7 Ϯ 9.8% reduction in eNOS expression in UA 2°and UA 3°. A similar decreasing eNOS regional expression gradient was observed in LP ewes. No eNOS regional expression gradient was observed in FOL or MP ewes because eNOS increased in UA 2°and UA 3°. In UA 2°and UA 3°, MP Ͼ LP ϭ FOL Ͼ LUT. Thus, with increasing UBF, FOL and pregnancy rises in SS may regulate eNOS protein expression in smaller diameter UAs. A decrease in LUT and LP UA 2°and UA 3°endothelial eNOS suggest a possible negative feedback mechanism due to downregulation of eNOS if SS is normalized. uterus; shear stress; endothelial nitric oxide synthase; ovarian; estrogen; progesterone UTERINE ARTERY (UA), but not systemic (renal) artery (RA) endothelial, endothelial nitric oxide (NO) synthase (eNOS) protein (29, 40) and mRNA (29) are elevated during the follicular phase of the ovarian cycle, in which the endogenous estrogen-to-progesterone ratio and uterine blood flow (UBF) are elevated (9, 11, 26). A low basal UBF level and a low estrogen-toprogesterone ratio characterize the luteal phase. Similar increases in eNOS protein levels were noted during the follicular phase of the menstrual cycle in women (31). Furthermore, these alterations in eNOS levels in the UA endothelium can be mimicked by exogenous administration of 17␤-estradiol and/or progesterone (35,36,40). [27][28][29]37,47) and its physiological second messenger cGMP (17,27,37) are increased during pregnancy. UA, but not systemic artery endothelial, eNOS protein (28,29,31,47) and mRNA (1, 29) expression and activity (27,31,46) also are elevated by pregnancy. UA eNOS protein levels are unchanged during late gestation, from day 110 to 142 of ovine pregnancy (28), although nitrite or nitrate (NO x ) levels increase with advancing gestational ages during the third trimester (29). The timing of either the gestational increase in UA eNOS expression or the circulating NO x levels during the second trimester of pregnanc...

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“…Placental NO maintains the myometrial relaxation and the vascular tone in the feto-placental circulation (Kublickiene et al 1997, Magness et al 1997. However, abnormal levels of NO are associated with diabetic-induced abnormalities such as pancreas damage, embryo, and fetal dysmorphogenesis, and diabetic vascular complications (Gonzalez et al 1999, Jawerbaum & González 2006, Nakagawa et al 2006.…”

Section: Discussionmentioning

confidence: 99%

The role of nitric oxide on matrix metalloproteinase 2 (MMP2) and MMP9 in placenta and fetus from diabetic rats

Pustovrh

Jawerbaum²,

White³

et al. 2007

Reproduction

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Matrix metalloproteinases (MMPs) play an important role in tissue remodeling that accompanies the rapid growth, differentiation, and structural changes of the placenta and several fetal organs. In the present study, we investigated whether the diabetic maternal environment may alter the regulatory homeostasis exerted by nitric oxide (NO) on MMPs activity in the feto-placental unit from rats at midgestation. We found that NADPH-diaphorase activity, which reflects the distribution and activity of NO synthases (NOS), was increased in both placenta and fetuses from diabetic rats when compared with controls. In addition, while a NO donor enhanced MMP2 and MMP9 activities, a NOS inhibitor reduced these activities in the maternal side of the placenta from control rats. This regulatory effect of NO was only observed on MMP9 in the diabetic group. On the other hand, the NO donor did not modify MMP2 and MMP9 activities, while the NOS inhibitor reduced MMP9 activity in the fetal side of both control and diabetic placentas. In the fetuses, MMP2 was enhanced by the NO donor and reduced by the NO inhibitor in both fetuses from control and diabetic rats. Overall, this study demonstrates that NO is able to modulate the activation of MMPs in the fetoplacental unit, and provides supportive evidence that increased NOS activity leads to NO overproduction in the feto-placental unit from diabetic rats, an alteration closely related to the observed MMPs dysregulation that may have profound implications in the formation and function of the placenta and the fetal organs.

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Role of nitric oxide in the regulation of vascular tone in pressurized and perfused resistance myometrial arteries from term pregnant women

Cited by 70 publications

References 17 publications

Vascular adaptations to pregnancy in mice: effects on myogenic tone

Vascular adaptations to pregnancy in mice: effects on myogenic tone

Endothelial vasodilator production by uterine and systemic arteries. IX. eNOS gradients in cycling and pregnant ewes

The role of nitric oxide on matrix metalloproteinase 2 (MMP2) and MMP9 in placenta and fetus from diabetic rats

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