Effects of estrogens and selective estrogen receptor modulators on vascular reactivity in the perfused mesenteric vascular bed

Abstract

Mark CJ, Tatchum-Talom R, Martin DS, Eyster KM. Effects of estrogens and selective estrogen receptor modulators on vascular reactivity in the perfused mesenteric vascular bed. Am J Physiol Regul Integr Comp Physiol 293: R1969-R1975, 2007. First published September 19, 2007; doi:10.1152/ajpregu.00260.2007.-Estrogens and selective estrogen receptor modulators (SERMs), such as raloxifene (RAL) and tamoxifen (TAM), acutely relax arteries, but the long-term effects of estrogens and SERMs on vascular reactivity in the mesenteric vasculature have not been well defined. In this study, we used an isolated, perfused mesenteric vascular bed technique to investigate the effect of chronic treatment of estrogens and SERMs on vascular reactivity of the mesenteric bed. Ovariectomized female SpragueDawley rats were treated by gavage with vehicle (control, 2-hydroxypropyl-␤-cyclodextrin), ethinyl estradiol, estradiol benzoate, equilin (EQ), TAM, or RAL for 3 wk. EQ and TAM increased vasoconstriction in response to all three vasoconstrictors tested (KCl, norepinephrine, and 5-HT). Ethinyl estradiol increased vasoconstriction in response to KCl and 5-HT, whereas responses to estradiol benzoate and RAL were less consistent. Only EQ (134 Ϯ 4 mmHg) and TAM (104 Ϯ 4 mmHg) changed mean arterial blood pressure compared with control (117 Ϯ 4 mmHg). These data demonstrate that 3-wk gavage treatment with estrogens and SERMs affects vascular reactivity in the mesenteric vascular bed. However, the three formulations of estrogen did not produce equivalent effects, and the effects of the SERMs were different from those of the estrogens. equilin; ethinyl estradiol; estradiol benzoate; tamoxifen; raloxifene CARDIOVASCULAR DISEASE (CVD) is one of the most common diseases in the industrialized world and is a major cause of human death (10). The incidence of CVDs, such as hypertension and atherosclerosis, is greater in men than in premenopausal women (13). Among women, the incidence of CVD is greater in postmenopausal women than premenopausal women (39). The loss of estrogen at the menopause is hypothesized to underlie the epidemiological link between menopause and increased cardiovascular risk. Thus it is important to continue to gain a better understanding of the action of estrogen on the vascular system. Alterations in vascular tone play a major role in the control of blood pressure (BP) and thereby the incidence of hypertension and CVD. 17␤-Estradiol has been shown to act acutely as a direct vasodilator (27). Conversely, Li and Stallone have shown that chronic 3-wk treatment with estrogen potentiated the contractile responses of the female rat aorta to vasopressin (24a). For this investigation, we chose a chronic 3-wk treatment with three formulations of estrogen and two selective estrogen receptor modulators (SERMs). The estrogens chosen for this study are among the most routinely used for research and therapeutic treatment. Ethinyl estradiol (EE) is used orally, either alone or with a progestin, in oral contraceptives (43). Equilin (EQ) is an...

Blood Pressure and Mesenteric Vascular Reactivity in Spontaneously Hypertensive Rats 7 Months After Gonadectomy

“…SHR were exsanguinated by aortic puncture under isoflurane anesthesia. The superior mesenteric artery was cannulated and the gut removed as previous described (25). Briefly, the isolated mesenteric vascular bed (MVB) was constantly perfused (5 ml/min) and superfused (0.2 ml/min) using two separate pumps with modified Krebs-Henseleit (in mM: 118 NaCl, 4.7 KCl, 1.2 MgCl 2 ·6H 2 O, 1.0 NaH 2 PO4, 2.6 CaCl 2 ·2H 2 O, 25 NaHCO3, 11.1 glucose; 37°C; pH 7.35-7.45), oxygenated with a 95% oxygen-5% carbon dioxide gas mixture.…”

“…On the other hand, Brandin reported that ovariectomy did not alter the mesenteric constrictor responses to norepinephrine in SHR (22). Previously we observed variable effects of estrogens on mesenteric vascular reactivity depending on the formulation of estrogen compounds administered to rats (25). Data concerning the effects of androgens on mesenteric vascular reactivity are relatively sparse.…”

A component of Premarin® enhances multiple cognitive functions and influences nicotinic receptor expression

“…Doses were adjusted to account for Δ 8 E1 and equilin being in its unconjugated form1, and to approximate the rat body weight equivalent of the 0.625 mg dose, which was used in the WHIMS and is what women are most commonly prescribed (Acosta et al, 2009b; Engler-Chiurazzi et al, 2009). The high doses for Δ 8 E1 and equilin were based on the only other available reports in the rat model using these hormones, wherein Δ 8 E1 decreased depolarization-induced cardiac synapse norepinephrine release, and equilin elevated vascular reactivity in the mesenteric vascular bed (Eskin et al, 2003; Mark et al, 2007). The medium doses of Δ 8 E1 and equilin were half of the high doses.…”

Estrogens and selective estrogen receptor modulators regulate gene and protein expression in the mesenteric arteries

“…Information on the effects of these SERMs in the vasculature remains limited and contradictory. Both exhibited positive effects on local blood flow in some (Leung et al, 2007) but not other (Mark et al, 2007) studies, and both tamoxifen and raloxifene increased the risk of venous thromboembolic events (Cuzick et al, 2003, Decensi et al, 2005). …”

“…The vasculature is clearly a target for estrogen (Ling et al, 2006; Miller and Duckles, 2008; Xing et al, 2009), and estrogens can directly affect vascular function (Li and Stallone, 2005; Li M., et al, 2008; Mark et al, 2007). Nevertheless, the precise effects of estrogen in the vasculature remain contradictory and controversial.…”