Growth hormone-induced blood pressure decrease is associated with increased mRNA levels of the vascular smooth muscle KATP channel

Abstract

Growth hormone (GH) deficiency is associated with abnormal vascular reactivity and development of atherosclerosis. GH treatment in GH deficient states restores systemic vascular resistance, arterial compliance, endothelium-dependent and endothelium-independent vasodilation, and may reverse markers of early atherosclerosis. However, very little is known about the molecular mechanisms underlying these effects. In the present study, male Sprague Dawley rats were hypophysectomized and treated for two weeks with GH (recombinant human GH, 2 mg/kg/day) or saline as s.c. injections twice daily. GH decreased aortic systolic blood pressure compared with saline-treated animals, while the diastolic blood pressure was not significantly changed. GH treatment increased cardiac output as determined by Dopplerechocardiography and the calculated systemic vascular resistance was markedly reduced. In order to identify GH-regulated genes of importance for vascular function, aortic mRNA levels were analyzed by the microarray technique and correlated to the systolic blood pressure levels. Using this approach, we identified 18 GHregulated genes with possible impact on vascular tone and atherogenesis. In particular, mRNA levels of the inwardly rectifying potassium channel Kir6·1 and the sulfonylurea receptor 2B, which together form the vascular smooth muscle ATP-sensitive potassium channel, were both upregulated by GH treatment and highly correlated to systolic blood pressure. Our findings establish a major role for GH in the regulation of vascular physiology and gene expression. Increased expression of the ATP-sensitive potassium channel, recently shown to be crucial in the regulation of vascular tone, constitutes a possible mechanism by which GH governs vascular tone.

The GH/IGF-1 Axis and Heart Failure

“…Recently, NO has been shown to modulate cardiac cytoskeletal functions by altering calcium myofilament responsiveness [70]. In addition, IGF-1 may cause vasorelaxation both by enhancing Na + /K + ATPase activity [71] and regulating gene expression of K ATP channel in vascular smooth cells [72]. This ATP-sensitive potassium channel consists of two subunits: the sulfonylurea receptor and the inwardly rectifying potassium channel, which could be critical in regulating vascular tone [73, 74].…”

Growth Hormone and Insulin-Like Growth Factor in Adults With Arterial Hypertension

“…Снижение концентрации ИФР в плазме у боль-ных с АГ отмечалось в большинстве [5,13], но не во всех проведенных исследованиях [12]. Одной из причин вариабельности полученных результатов может быть недооценка взаимозависимости содержа-ния ГР и ИФР в крови и развития ожирения у боль-ных с АГ.…”

Altered ATP-sensitive potassium channels may underscore obesity-triggered increase in blood pressure1

“…The opening of arterial K ATP channels causes membrane hyperpolarization, a decrease in Ca 2+ influx through voltage-dependent L-type Ca 2+ channels, and vasorelaxation [17,18] . Growth hormones may decrease blood pressure via increased K ATP channel mRNA in VSMC [19] . These data clearly show that inhibited K ATP channels increase blood pressure.…”