Vascular adaptations to pregnancy in mice:  effects on myogenic tone

Veerareddy, Sukrutha; Cooke, Christy‐Lynn M.; Baker, Philip N.; Davidge, Sandra T.

doi:10.1152/ajpheart.00593.2002

Cited by 57 publications

(66 citation statements)

References 40 publications

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“…Previous studies (16,38,39,51) have shown a decrease in pressure-induced myogenic tone of uterine, mesenteric, and renal arteries in pregnant mice and rats. In contrast, myogenic reactivity of myoendometrial radial uterine arteries was found to be increased in pregnant rats (41).…”

Section: Discussionmentioning

confidence: 91%

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Pregnancy attenuates uterine artery pressure-dependent vascular tone: role of PKC/ERK pathway

Xiao

Buchholz²,

Zhang³

2006

American Journal of Physiology-Heart and Circulatory Physiology

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]i was significantly greater for pressure-induced contraction of NPUA than that of PUA. Inhibition of PKC by calphostin C significantly attenuated the pressure-induced vascular tone and eliminated the difference of myogenic responses between NPUA and PUA. In contrast, the MAPKK (MEK) inhibitor PD-098059 had no effect on NPUA but significantly enhanced myogenic responses of PUA. In the presence of PD-098059, there was no difference in pressure-induced myogenic responses between NPUA and PUA. The results suggest that pregnancy downregulates pressure-dependent myogenic tone of the uterine artery, which is partly due to increased MEK/ERK activity and decreased PKC signal pathway leading to a decrease in Ca 2ϩ sensitivity of myogenic mechanism in the uterine artery during pregnancy.sheep; protein kinase C; extracellular signal-regulated kinase PREGNANCY IS ASSOCIATED WITH a significant increase in uterine blood flow that optimizes the delivery of oxygen and substrates to the developing fetus via the placenta. The adaptations in the uterine circulation to pregnancy are complex and are mediated in part by enhanced vasodilation and vascular remodeling. Previous studies (3,47,54,57) have focused on the endothelial adaptation and have shown an increase in endothelial nitric oxide synthesis/release in the uterine artery during pregnancy. The adaptation of smooth muscle contractile mechanisms is less clear. Pressure-dependent myogenic contraction is an important physiological mechanism that regulates basal vascular tone and is a significant contributor to the modulation of blood flow (6, 21). Myogenic response has been found as either increased or decreased in uterine arteries of pregnant, compared with nonpregnant, rats, mice, and rabbits (5, 42, 51).Although arterial myogenic behavior has been studied intensively for decades, the mechanisms by which vascular smooth muscle cells respond to changes in intraluminal pressure are still not fully understood. Previous studies (17,29,37) indicated that myogenic tone was highly dependent on an elevation of intracellular free Ca 2ϩ concentration ([Ca 2ϩ ] i ). However, it has also been demonstrated that Ca 2ϩ sensitization mechanisms contribute to myogenic tone (28,30,49,50). Activation of various kinase cascades regulating Ca 2ϩ sensitivity of the contractile apparatus may modulate the level of arteriolar myogenic reactivity (8, 21). PKC has been proposed to play an important role in the regulation of basal vascular tone and arterial caliber, the major determinants of blood flow (6, 41, 44). Pressure-induced activation of PKC has been proposed to induce myogenic tone without additional increases in Ca 2ϩ concentrations or myosin light chain (MLC 20 ) phosphorylation (18, 31). Our recent studies have also demonstrated in ovine uterine arteries that activation of PKC causes sustained contractions in the absence of changes in [Ca 2ϩ ] i and MLC 20 phosphorylation levels (56) and that the PKC-mediated contraction is significantly attenuated in the uterine artery during pregnancy (...

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Section: Discussionmentioning

confidence: 91%

“…Myogenic response has been found as either increased or decreased in uterine arteries of pregnant, compared with nonpregnant, rats, mice, and rabbits (5,42,51).…”

mentioning

confidence: 99%

Pregnancy attenuates uterine artery pressure-dependent vascular tone: role of PKC/ERK pathway

Xiao

Buchholz²,

Zhang³

2006

American Journal of Physiology-Heart and Circulatory Physiology

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“…Additionally, reduced activity of endothelial NOS and, perhaps, nitric oxide bioavailability along with impaired vascular function in offspring from DR dams has been demonstrated [5,41]. Our previous studies showed that endothelial removal from uterine arteries of pregnant mice resulted in a comparable increase in myogenic responses to that found by NOS inhibition [42]. Therefore, we speculate that impaired endothelial function causes a relative deficiency of nitric oxide-mediated vasodilation during pregnancy and manifests as increased myogenic reactivity in the offspring of DR rat dams.…”

Section: Fig 2 Myogenic Responses In Radial Uterine (A) and Mesentementioning

confidence: 94%

Increased Myogenic Responses in Uterine but not Mesenteric Arteries from Pregnant Offspring of Diet-Restricted Rat Dams1

Hemmings¹,

Veerareddy²,

Baker³

et al. 2005

Biology of Reproduction

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Results of epidemiological and animal studies suggest a link between poor in utero growth and cardiovascular disease in adult offspring. Few studies, however, have examined the effects of maternal undernutrition on the vasculature of pregnant female offspring, and to our knowledge, no studies have examined myogenic responses, which are essential to vascular tone development, in these animal models. Thus, myogenic responses were assessed in radial uterine arteries of pregnant female offspring to determine if diet restriction during pregnancy could contribute to transgenerational effects. These results were compared to those in mesenteric arteries, which greatly contribute to peripheral vascular resistance. Myogenic responses in the presence and absence of inhibitors for nitric oxide synthase (NOS) and prostaglandin H synthase (PGHS) were measured in arteries isolated from pregnant, 3-mo-old female offspring of control-fed (C(off)) and globally diet-restricted (DR(off)) rat dams. Although no differences were found in pregnancy weight gain, litter size, or fetal weights, placental size was significantly reduced in DR(off) compared to C(off). Enhanced myogenic reactivity was observed at the highest pressure tested (110 mm Hg) in uterine, but not in mesenteric, arteries from DR(off) compared to C(off). Inhibition of NOS, but not of PGHS, significantly increased myogenic responses in uterine arteries at pressures greater than 80 mm Hg in C(off) but, interestingly, not in DR(off) compared to untreated uterine arteries. Thus, impaired uterine vascular function in diet-restricted pregnant rat dams, which leads to similar impairment in their pregnant offspring, may be a mechanism through which transgenerational effects of unhealthy pregnancies occur.

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“…On day 20 of pregnancy (term ϭ 22 d) dams were killed under surgical plane anesthesia (intraperitoneal injection of sodium pentobarbital, [Somnotol, MTC Pharmaceuticals, Ontario, Canada, 42.25 mg/kg body weight]), the abdominal cavity was opened, and the fetuses were rapidly delivered by caesarean section and placed in cold Dulbecco's medium. Dulbecco's medium contained Dulbecco's Modified Eagle medium base (Sigma Chemical Co.), supplemented with 1 mmol/L sodium pyruvate, 25 mmol/L sodium bicarbonate, 5 mmol/L HEPES, 5 mmol/L glucose, and nutrient amino acids and vitamins that improved viability of vessels studied in vitro (21).…”

Section: Methodsmentioning

confidence: 99%

Maternal Nutrient Restriction Reduces Carotid Artery Constriction Without Increasing Nitric Oxide Synthesis in the Late Gestation Rat Fetus

et al. 2005

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Chronic reduction in substrate delivery to the fetus may induce redistribution of fetal cardiac output to maintain nutrient delivery to vital organs, including the brain. Reduced vasoconstriction, in conjunction with increased local synthesis of nitric oxide may contribute to "brain sparing." The authors hypothesized that maternal undernutrition would reduce vasoconstrictor responses in fetal carotid arteries due to increased nitric oxide. Timed pregnant Sprague-Dawley rats were randomized on day 0 of pregnancy to control (C) or nutrient restricted (NR) diet. Dams were killed on day 20 of pregnancy. Fetal carotid artery responses were assessed using a pressurized myograph system. Fetal body weight was reduced by NR diet. In NR fetuses, liver, lung, kidney, and heart weights were lower, whereas proportional brain weight was greater. Carotid artery constriction to endothelin-1 was similar in both groups; however, phenylephrineinduced constriction was decreased in NR arteries. Arteries from control fetuses constricted in response to increasing concentrations of L-NAME, whereas arteries from NR did not. There was also no effect of L-NAME on constriction to phenylephrine in arteries from NR fetuses. Our study indicates that the reduced carotid artery vasoconstriction to phenylephrine in NR fetuses, which is consistent with the maintenance of fetal brain blood flow, was not mediated by enhanced nitric oxide. Reduced phenylephrine but not endothelin-1-induced constriction suggests specific effects on adrenergic carotid artery function, which may implicate this pathway in the vascular adaptation to fetal undernutrition. Intrauterine growth restriction (IUGR) involves a failure of the fetus to achieve its genetic potential for growth. Fetal growth restriction has significant impact on pregnancy outcome and neonatal health status where IUGR fetuses demonstrate increased neonatal mortality, morbidity, and prematurity rates (1,2). The pathophysiological processes that result in fetal growth restriction are multiple and diverse; globally one cause of growth restriction is thought to be malnutrition. Human populations studied after acute maternal malnutrition during pregnancy have demonstrated both impaired fetal growth and long-term consequences for adult health (3-7).Compromised fetuses undergo cardiovascular adaptation to preserve blood flow to vital organs, such as the heart, brain, and adrenal glands, at the expense of peripheral tissues (8,9). This adaptation may involve changes in the regional vascular response to vasoconstrictor, and dilator factors, which serves to redistribute cardiac output. It has previously been demonstrated in fetal sheep that maternal nutrient restriction impaired endothelial-dependent relaxation, and vascular sensitivity to nitric oxide in small arteries from the femoral vascular bed (10,11); however, the effects of undernutrition on the function of arteries supplying blood flow to the brain are not known.During acute hypoxia, the fetal redistribution of cardiac output, and maintenance of brai...

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Vascular adaptations to pregnancy in mice: effects on myogenic tone

Cited by 57 publications

References 40 publications

Pregnancy attenuates uterine artery pressure-dependent vascular tone: role of PKC/ERK pathway

Pregnancy attenuates uterine artery pressure-dependent vascular tone: role of PKC/ERK pathway

Increased Myogenic Responses in Uterine but not Mesenteric Arteries from Pregnant Offspring of Diet-Restricted Rat Dams1

Maternal Nutrient Restriction Reduces Carotid Artery Constriction Without Increasing Nitric Oxide Synthesis in the Late Gestation Rat Fetus

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