Effects of pregnancy and hormone treatments on pressor response to angiotensin II in conscious rats

Nakamura, Toshimichi; Matsui, Kazuo; M, Ito; Yoshimura, Toshihiro; Kawasaki, N.; Fujisaki, Shunichi; Okamura, Hitoshi

doi:10.1016/s0002-9378(88)80186-8

Cited by 20 publications

(12 citation statements)

References 15 publications

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“…15 We wondered whether progesterone also exhibited direct vascular effects, independently of estrogen. Since the early work of Landau and Lugibihl, who demonstrated natriuretic effects of P 21 more than 4 decades ago, progesterone has been reported to lower BP in hypertensive men and postmenopausal women 4,7 ; to blunt the pressor response to Ang II in ovariectomized rats (which estrogen does not) 8,9 ; and to alter adrenergic activity, 22 decreasing systemic vascular resistance in normal women 23,24 and increasing cardiac output.…”

Section: Discussionmentioning

confidence: 99%

“…Previous mechanistic studies have focused on cardiovascular protective effects attributable to estrogens, but accumulating evidence suggests that progesterone independently of estrogen also exerts a protective influence on the vasculature. 3 Thus progesterone receptors have been localized in the myocardium 4 and in peripheral vascular tissue, 5 and administration of progesterone lowers BP in humans, 3,6 blunts the pressor response to Ang II in human pregnancy, 7 and inhibits Ang II action in rats in some, 8,9 but not all, reports. 10,11 We intended to further define the vascular actions of progesterone and to study potential mechanism(s) underlying these effects.…”

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confidence: 99%

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Vascular Effects of Progesterone

et al. 2001

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Abstract-Vascular actions of progesterone have been reported, independently of estrogen, affecting both blood pressure and other aspects of the cardiovascular system. To study possible mechanisms underlying these effects, we examined the effects of P in vivo in intact rats and in vitro in isolated artery and vascular smooth muscle cell preparations. In anesthetized Sprague-Dawley rats, bolus intravenous injections of P (100 g/kg) significantly decreased pressor responses to norepinephrine (0.3 g/kg). In vitro, progesterone (10 Ϫ8 to 10 Ϫ5 mmol/L) produced a significant, dose-dependent relaxation of isolated helical strips, both of rat tail artery precontracted with KCl (60 mmol/L) or arginine vasopressin (3 nmol/L), and of rat aorta precontracted with KCl (60 mmol/L) or norepinephrine (0.1 mol/L). In isolated vascular smooth muscle cells, progesterone (5ϫ10 Ϫ7 mol/L) reversibly inhibited KCl (30 mmol/L) -induced elevation of cytosolic-free calcium by 64.1Ϯ5.5% (PϽ0.05), and in whole-cell patch-clamp experiments, progesterone (5ϫ10 Ϫ6 mol/L) reversibly and significantly blunted L-type calcium channel inward current, decreasing peak inward current to 65.7Ϯ4.3% of the control value (PϽ0.05). Our results provide evidence that progesterone is a vasoactive hormone, inhibiting agonist-induced vasoconstriction. The data further suggest that progesterone effects on vascular tissue may, at least in part, be mediated by modulation of the L-type calcium channel current activity and, consequently, of cytosolic-free calcium content. Key Words: progesterone Ⅲ intracellular calcium Ⅲ vascular smooth muscle Ⅲ sex steroid hormones Ⅲ L-type calcium channel Ⅲ hypertension Ⅲ menopause I t is well established that premenopausal women are at lower risk of developing hypertension and coronary heart disease than men of the same age and that the cardiovascular risk increases only after the cessation of ovarian function. 1 Conversely, pregnancy is associated with lower blood pressure (BP), despite elevated circulating angiotensin II (Ang II) levels and sodium retention. 2 Although the mechanism(s) underlying these observations are still poorly understood, a critical role for dramatic changes in the sex steroid environment is widely presumed. Previous mechanistic studies have focused on cardiovascular protective effects attributable to estrogens, but accumulating evidence suggests that progesterone independently of estrogen also exerts a protective influence on the vasculature. 3 Thus progesterone receptors have been localized in the myocardium 4 and in peripheral vascular tissue, 5 and administration of progesterone lowers BP in humans, 3,6 blunts the pressor response to Ang II in human pregnancy, 7 and inhibits Ang II action in rats in some, 8,9 but not all, reports. 10,11 We intended to further define the vascular actions of progesterone and to study potential mechanism(s) underlying these effects. Therefore, we evaluated the short-term effects of progesterone in a variety of circumstances: on BP in anesthetized rats, on vascular contra...

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

Vascular Effects of Progesterone

et al. 2001

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“…Estrogen impairs constriction and augments dilation of arteries and attenuates the pressor responsiveness to several vasoconstrictors (Sudhir et al 1995) similar to the reduced responsiveness that occurs in normal pregnancy (Nakamura et al 1988, Novak & Kaufman 1991. Progesterone may also be implicated in pregnancy refractoriness to angiotensin II.…”

Section: Introductionmentioning

confidence: 92%

“…Progesterone may also be implicated in pregnancy refractoriness to angiotensin II. Progesterone down-regulates angiotensin II receptors in rat uterine smooth muscle independently of angiotensin II levels and it, directly or through a metabolite, might have the effect on vascular receptors in humans (Nakamura et al 1988).…”

Section: Introductionmentioning

confidence: 98%

Regulation of cardiac oxytocin system and natriuretic peptide during rat gestation and postpartum

Mukaddam‐Daher

Jankowski²,

Wang³

et al. 2002

Journal of Endocrinology

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We have recently uncovered the presence of an oxytocin system in the heart and found that oxytocin is a physiological regulator of atrial natriuretic peptide (ANP), a diuretic, natriuretic and vasodilator cardiac hormone. However, dynamic changes in these systems during gestation, when mechanisms of volume and pressure homeostasis are altered, are not clear. Accordingly, ANP, oxytocin and oxytocin receptors were evaluated in rat hearts and plasma at three stages of gestation (7, 14 and 21 days) and at 2 and 5 days postpartum. Compared with non-pregnant controls, plasma ANP was elevated in midgestation, but significantly decreased at term (21 days), to increase again postpartum. Right and left atrial ANP mRNA levels were not altered throughout gestation but increased by 1·5-to 2-fold postpartum (P<0·01). At term, ANP content in right (8·7 1·2 vs 12·7 1·1 µg/mg protein, P<0·04) and left (3·5 0·6 vs 8·5 2·0 µg/mg protein, P<0·01) atria increased. These findings imply that decreased plasma ANP at term results from inhibition of release rather than decreased synthesis. In parallel, oxytocin, a stimulator of ANP release, decreased in left atria at day 7 to 50% of non-pregnant levels and remained low throughout gestation. Oxytocin receptor mRNA increased in left atria at 7 and 14 days of gestation by 2-and 5-fold respectively, but decreased at 21 days to lower than non-pregnant levels to increase again (3-fold) postpartum. The changes in oxytocin receptor expression at term and postpartum paralleled oxytocin receptor protein determined by Western blot. These results imply that pregnancy is associated with dynamic changes in the cardiac oxytocin system (peptide and/or receptors), which may influence natriuretic peptide release. Together, these peptides would act on their receptors in the heart, vasculature and kidneys to maintain vascular tone and renal function throughout gestation and postpartum.

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“…The pressor response to angiotensin II was examined on day 13 by a previously reported method [7]. Each animal was anesthetized with diethyl ether, and polyethylene catheters (3 french) were placed in the femoral artery and vein.…”

Section: Methodsmentioning

confidence: 99%

Nitric Oxide Affects Angiotensin II Pressor Response: Possible Mechanism of Attenuated Pressor Response during Pregnancy and Etiology of Pregnancy-Induced Hypertension

Maeda

Yoshimura

Ohshige

et al. 2000

Gynecol Obstet Invest

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Objective: To investigate the mechanism of attenuated pressor responses to several vasoconstrictors during gestation, we sought to characterize the effects of N^G-monomethyl-L-arginine (L-NMMA) and L-arginine (L-Arg) on the pressor response to the infusion of angiotensin II in rats. Methods: L-NMMA and L-Arg were infused intraperitoneally into rats at a constant rate by means of an osmotic minipump. The L-NMMA group received an infusion of L-NMMA (3 mg/day) daily for 13 days, whereas the L-NMMA plus L-Arg group received L-NMMA (3 mg/day) daily for 4 days, followed by L-NMMA plus L-Arg (12 mg/day) daily for 9 days. Sham-operated rats served as controls. The animals were anesthetized on day 13, and catheters were placed into the femoral artery and vein. After the animals had recovered from anesthesia, the pressor response to intravenous bolus doses of angiotensin II (50, 100, 200, and 400 ng/kg) were determined after recovery from anesthesia. Results: While the baseline mean arterial blood pressure was not affected by L-NMMA, with or without L-Arg, the pressor response to angiotensin II in the L-NMMA group was significantly increased as compared with that in the control group, at doses of 50, 100, and 200 ng/kg. The response of the L-NMMA plus L-Arg group did not differ significantly from that of the control group. Conclusion: Results indicate that the infusion of a nitric oxide synthase inhibitor, at a dose insufficient to produce hypertension, increases the pressor response to angiotensin II.

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Effects of pregnancy and hormone treatments on pressor response to angiotensin II in conscious rats

Cited by 20 publications

References 15 publications

Vascular Effects of Progesterone

Vascular Effects of Progesterone

Regulation of cardiac oxytocin system and natriuretic peptide during rat gestation and postpartum

Nitric Oxide Affects Angiotensin II Pressor Response: Possible Mechanism of Attenuated Pressor Response during Pregnancy and Etiology of Pregnancy-Induced Hypertension

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