Sensitivity to Ca2+ and the Effects of a Calcium Channel Antagonist in Resistance Vessels from Two Strains of Genetically Hypertensive Rat

Influence of age on the relaxation induced by nifedipine in aorta from spontaneously hypertensive and Wistar Kyoto rats

“…They suggest that an intracellular effect of nifedipine in this strain, along with Ca2+ influx inhibition, cannot be discounted. However, Cassie et al (1990) reported that the sensitivity of diltiazem to inhibit K' -induced contractions was greater in WKY than in SHR mesenteric arteries from adult rats, suggesting a minor Ca2+ reflux dependency, through Ca2+ channels or an alteration of these channels, in SHR vessels. The increased vascular effect of nifedipine in SHR segments, described by different authors (Pederssen, Mikkelsen & Anderson, 1978;Pederssen, 1979;Atkinson et al, 1988), may be because the calcium regulatory mechanisms undergo changes during the development of hypertension than enhances the extracellular Ca2+ -dependency (Pederssen, 1979;Dong & Wadsworth, 1986;Atkinson et al, 1988;Marin, 1993).…”

“…These data may provide the basis of the wide use and the greater potency of Ca2 + -channel antagonists in elderly patients (Wei, 1989;Wadsworth, 1990: Calvo-G6mez et a/., 1992). In addition, these facts may reflect the association of age with alter- -SHR (7) -WKY (7) ANOVA -SHR (7) -WKY (7) -1 ANOVA -SHR (8) -WKY (7) ANOVA p < 0.0001 ation on transmembranal extracellular Ca2 + exchange, such as the increase in Ca2'-dependency (Pederssen, 1979) or Ca' + -sensitivity (Cassie et al, 1990) observed in rat aorta and mesenteric arteries, respectively. The enhancement in the nifedipine sensitivity with age may result from an increase in dihydropyridine binding and affinity, as reported previously (Dillon, Gu & Nayler, 1989).…”

“…Hypertension (Khali, Logde, Saida, Gelband & Van Breemen, 1990;Shepherd, 1990;Wadsworth, 1990;Marin, 1993) and ageing (Docherty, 1990;Wadsworth, 1990;Folkow & Svandborg, 1993) are two conditions that can modify the response elicited by different drugs. In both conditions, the endothelium-dependent relaxations are reduced (Hongo et al, 1988;Vanhoutte, 1988;Shepherd, 1990;Murohara, Ysue, Ohgushi, Sakaino & Jougasaki, 1991;Lucher, Boulanger, Dohi & Yang, 1992;Marin, 19931, and the sensitivity to Ca2+ and the vasodepressor effects of Ca2+ -channel antagonists are increased (Wanstall & O'Donnell, 1988, 1989Cassie, Cross, Phelan & Millar, 1990;Khalil et al, 1990;Wadsworth, 1990;Grammas, Giacomelli, Bessert, Diglio & Wiener, 1991;Marin, 1993). This implies that Ca' + influx through either voltage-gated (VGCCs) or receptor-operated (ROCs) Ca2+ channels, and the sensitivity of these channels to Ca' + -channel antagonists may be altered in both situations (Aoki & Asano, 1986;Atkinson et al, 1988;Wanstall & O'Donnell, 1988, 1989Wadsworth, 1990).…”

Effects of Cilazapril on the Structure of Mesenteric Resistance Arteries of New Zealand Genetically Hypertensive and Normotensive Control Rats

“…Hypertension in the New Zealand GH rat is associated with vascular and cardiac hypertrophy (Cassie et al 1990;Ledingham & Millar 1993) and it seemed possible that the mitogenic action of angiotensin I1 might contribute to these changes. This possibility has been studied by treating genetically …”

“…There are a number of studies with Japanese spontaneously hypertensive rat (SHR) reporting the prevention of hypertension by treatment with angiotensinconverting enzyme (ACE) inhibitors, and also of regression of abnormal vessel structure. Hypertension in the New Zealand GH rat is associated with vascular and cardiac hypertrophy (Cassie et al 1990;Ledingham & Millar 1993) and it seemed possible that the mitogenic action of angiotensin I1 might contribute to these changes.…”