Membrane mechanisms in arterial hypertension.

Abstract

SUMMARY The purpose of this review is to focus on alterations in vascular muscle membrane potentials (E m ), ionic permeabilities, and ionic transport systems which may either contribute to or be a consequence of the hypertensive state. Three models of hypertension are discussed: 1) deoxycorticosterone-salt (DOCA-salt)-induced hypertension; 2) low-renin (presumably volume expanded) renal hypertension (LRRH); and 3) the spontaneously hypertensive rat (SHR) of the Okamoto-Aoki KyotoWistar strain and its normotensive genetic control (WKY). The importance of studying all possible mechanisms of increased contraction in vascular smooth muscle is stressed. (Hypertension 5: 404-408, 1983) KEY WORDS • DOCA-salt hypertension • low-renin renal hypertension • spontaneously hypertensive rat • vascular smooth muscle • ionic permeability transport systems • blood pressure regulation • membrane potential A LTHOUGH neural and humoral factors influence both central and peripheral sites to regulate arterial pressure (Brody, 1 Abboud 2 ), the final common pathway for the control of vascular reactivity, and ultimately peripheral vascular resistance, lies at the level of the vascular smooth muscle cell. Thus, knowledge of the membrane processes responsible for vascular muscle cell activation is crucial in understanding the complete scope of blood pressure regulation. Furthermore, it is important to recognize the differences found in different blood vessels (Hermsmeyer,(3)(4) ). For valid conclusions to be drawn, the same vessel should be compared in hypertensive and normotensive animals. Mechanisms worked out in a particular blood vessel can be rigorously applied only to that particular vessel, unless others of interest have also been vigorously investigated. For a comprehensive theory of altered vascular muscle membrane function, the same measurements should be carried out on each vessel of interest. As data from different blood vessels are only available for some of the alterations found, it is difficult to draw more than qualified conclusions about the generality of differences.This overview will encompass the following concepts regarding the vascular muscle cell membrane and its control over force development in the hypertensive vs normotensive state: differences between in vivo and in vitro membrane potential (E m ), including the effects of an intact sympathetic innervation; altered ionic permeabilities in hypertensive vascular smooth muscle and the concomitant effect on vascular reactivity; and alterations in energy-dependent electrogenic ion transport as a function of humoral factors, innervation, or intrinsic muscle properties in vascular muscle cells from animals with hypertension of three different origins.

Hypertensive mechanisms associated with centrally administered aldosterone in dogs.

“…These neurogenic influences could stem from alterations in norepinephrine release and uptake 19 or changes in membrane potential of vascular smooth muscle. 20 The vascular smooth muscle of the spontaneously hypertensive rat has been shown to have a less negative resting membrane potential, a reduced K + equilibrium potential, and an enhanced electrogenic component to the resting membrane potential. These aberrations are associated with increased adrenergic influence on the vasculature.…”

Differences in norepinephrine activation and diltiazem inhibition of calcium channels in isolated rabbit aorta and mesenteric resistance vessels.

“…These observations, along with the observation that the sustained phase of agonist-induced contraction of arteries generally is dependent upon extracellular Ca ++ (Bohr, 1963;Hink, 1964;Flaim and Zelis, 1982;Loutzenhiser et al, in press), led to the hypothesis that NE could stimulate Ca ++ entry into arterial smooth muscle through receptoroperated channels (ROC) rather than potential sensitive Ca ++ channels [PSC (Bolton, 1979;van Breemen et al, 1979)]. However, in many arterial preparations, agonists have been found to produce at least some degree of depolarization Haeusler, 1978;Hermsmeyer et al, 1981;Mulvany et al, 1982;Harder and Hermsmeyer, 1983). Nevertheless, three further lines of evidence which support the hypothesis that NE could stimulate Ca ++ entry through ROC in the isolated rabbit aorta are as follows: (1) 45 Ca influx stimulated by NE (10~5 M) is additive to that stimulated by 80 ITIM K + (Meisheri et al, 1981); (2) 45 Ca influx induced by 80 mM K + is selectively inhibited over that stimulated by 10~5 M NE when organic Ca ++ antagonists (Meisheri et al, 1981; or dibutyryl cAMP (Meisheri and van Breemen, 1982) are employed to inhibit Ca ++ entry; and (3) the <5 Ca influx stimulated by the new "Ca ++ channel agonist* Bay K8644 is additive to that stimulated by 10~5 M NE, but not to that stimulated by 80 mM K + (Yamamoto et al, 1984).…”

The role of calcium in genetic hypertension.

“…The underlying mechanism is not defined but, hypothetically, is most likely related to a generalized defect in membrane calcium regulation 105 that is genetically transmitted rather than acquired as a consequence of the hypertension. The precise relation, if any, of altered membrane permeabilities to other ions, 129 in particular sodium, 130 " 135 is not clear. As shown in Figure 1, a plausible working hypothesis could integrate the concepts of Dahl, 133 de Wardener and MacGregor, 134 Bianchi and co-workerS) i36-iw Blaustein and Hamlyn, 130 and others.…”