The influence of oestrogen and progesterone on the actions of two calcium entry blockers in the rat uterus

Downing, Sandra J.; Hollingsworth, Michael A.; Miller, Marilyn

doi:10.1677/joe.0.1180251

Cited by 10 publications

(3 citation statements)

References 19 publications

(36 reference statements)

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“…4 In pregnancy, progesterone also augments nifedipine-induced inhibition of uterine contractions. 31 Mechanistically, under our experimental conditions, these effects of progesterone cannot easily be attributed to a genomic effect, because this presupposes a significant latency period, whereas our observations, at least in the in vitro experiments, were of a more immediate type. Because some latency period was observed in the in vivo experiments, the potential contribution of baroreflex and other mechanisms cannot be ruled out.…”

Section: Discussionmentioning

confidence: 61%

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: 61%

Vascular Effects of Progesterone

et al. 2001

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“…Stice et al (1987a,b) reported that oestradiol decreases calcium entry into uterine vascular smooth muscle cells. Downing et al (1988) observed that the inhibitory effect of nifedipine, a calcium entry blocker, was enhanced by oestradiol in the rat uterine artery. Sandahl et al (1978) reported in the rat that nifedipine, a potential-sensitive calcium channel blocker, caused an increase in uterine arterial flow.…”

Section: Discussionmentioning

confidence: 98%

Endothelium‐independent relaxation of rabbit coronary artery by 17β‐oestradiol in vitro

Jiang

Sarrel

Lindsay

et al. 1991

British J Pharmacology

350

154

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1 We assessed the relaxant effect of 17f,-oestradiol (10 -, 10-6 and 10-M) on rabbit isolated coronary arteries precontracted with prostaglandin F2,, (3 x 10-6M), high extracellular potassium (30mM) and Bay K 8644 (10-6M) plus high extracellular potassium (15 mM) by measuring isometric tension. 17fl-Oestradiol (10-6 and 10-5M) induced significant relaxation in coronary arteries from male and female rabbits. No differences were seen between arteries with or without endothelium. There were also' no differences between coronary arteries isolated from male and female rabbits. 2 Inhibitors of endothelium-derived relaxing factor and vasodilator prostanoids, namely, reduced haemoglobin, Nw-nitro-L-arginine methyl ester and indomethacin, did not affect the relaxation induced by 17fl-oestradiol in endothelium-intact coronary arteries.3 Methylene blue, an inhibitor of guanylate cyclase, did not affect the coronary artery relaxation induced by 17/1-oestradiol. 4 The' calcium concentration-dependent contraction curve in potassium-depolarization medium was shifted to the right by 17fl-oestradiol (10-6 and 10-5M) in the rabbit coronary artery and rat aorta. The -log EC50 s of calcium in control and after incubation with 17fi-oestradiol (10-6 and 10 -M) were 3.7 + 0.09, 3.1 + 0.10 and 2.8 + 0.08 respectively in rabbit coronary arteries and 3.8 + 0.11, 3.3 + 0.14 and 2.9 + 0.15 in rat aorta. 5 The results indicate that 17fi-oestradiol induces rabbit coronary artery relaxation by an endotheliumindependent mechanism in vitro. A calcium antagonistic property may be involved in the mechanism of rabbit coronary arterial relaxation by 17fi-oestradiol.

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“…Effect of 17P-oestradiol on 'Ca 1 7P-Oestradiol has been shown to enhance the inhibitory effect of nifedipine, a Ca2" channel antagonist, on arterial smooth muscle contraction and this enhancement can be reversed by increasing the external Ca2" (Downing et al, 1988). It has also been reported that 4-hydroxylated oestradiol reduced the Ca2l uptake in uterine smooth muscle pos- sibly by affecting the potential-sensitive Ca2" channel (Stice et al, 1987a,b).…”

Section: Discussionmentioning

confidence: 99%

Effect of 17β‐oestradiol on contraction, Ca²⁺ current and intracellular free Ca²⁺ in guinea‐pig isolated cardiac myocytes

Jiang

Poole‐Wilson

Sarrel

et al. 1992

British J Pharmacology

239

121

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4 17P-Oestradiol (10 and 30 SM) decreased the peak inward Ca2+ current (ICa), which was sensitive to [Ca2+]0, dihydropyridines and isoprenaline, to 59 ± 3% and 39 + 5% (n = 7-9, P<0.01) respectively, without producing any significant change in the shape of the current-voltage relationship.5 The recovery time of ICa from inactivation was delayed by 17p-oestradiol (10 tiM). The inhibitory effect of 17p-oestradiol on ICa was less at a holding potential of -80 mV than at -40 mV.

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The influence of oestrogen and progesterone on the actions of two calcium entry blockers in the rat uterus

Cited by 10 publications

References 19 publications

Vascular Effects of Progesterone

Vascular Effects of Progesterone

Endothelium‐independent relaxation of rabbit coronary artery by 17β‐oestradiol in vitro

Effect of 17β‐oestradiol on contraction, Ca²⁺ current and intracellular free Ca²⁺ in guinea‐pig isolated cardiac myocytes

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The influence of oestrogen and progesterone on the actions of two calcium entry blockers in the rat uterus

Cited by 10 publications

References 19 publications

Vascular Effects of Progesterone

Vascular Effects of Progesterone

Endothelium‐independent relaxation of rabbit coronary artery by 17β‐oestradiol in vitro

Effect of 17β‐oestradiol on contraction, Ca2+ current and intracellular free Ca2+ in guinea‐pig isolated cardiac myocytes

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Effect of 17β‐oestradiol on contraction, Ca²⁺ current and intracellular free Ca²⁺ in guinea‐pig isolated cardiac myocytes