Dissociation between calcium influx blockage and smooth muscle relaxation by nifedipine in spontaneously hypertensive rats.

Abstract

Aortic smooth muscle isolated from spontaneously hypertensive rats (SHR) and normotensive, agematched Wistar Kyoto rats (WKY) was precontracted by potassium chloride. The relaxant effect of nifedipine (NIF) was much more pronounced in SHR than in WKY, while the relaxation produced by nitroglycerin (NTG) was similar in both tissues. EC 50 s were (in -log | M | ) NIF: SHR 13.1 ± 0.4 and WKY 9.4 ± 0. 50 for 5.62 ± 0.09 in SHR and 6.07 ± 0.07 in NR, p<0.05). These data suggest that 1) the more pronounced relaxant action of NIF on SHR aortas cannot be explained by its effect on Ca 2+ influx, since both effects were dissociated in these vessels; and 2) the mechanism for NIF-dependent relaxation in SHR appears to be located not at the sarcolemmal but at some intracellular level. In this respect, a reduced calmodulin content in SHR arteries, along with an anticalmodulin action of NIF, could explain both the lesser sensitivity to Ca 2+ and the greater sensitivity to NIF that was found in SHR aortas. (Circulation Research 1987;60:367-374)

Mechanisms involved in the increased vascular resistance in hypertension

“…Hypertension may be accompanied by an enhancement in the sensitivity of peripheral resistance beds to Ca2+ antagonists, since the inhibition of a-adrenoceptor-mediated pressor responses by nicardipine is usually greater in SHR than WKY rat (Atkinson et al., 1988). The fact that the relaxant effect of nifedipine is more pronounced in aortic smooth muscle from SHR than from WKY supports these findings (Rinaldi, Cattaneo, Mattiazzi & Cingolani, 1987). However, the efficacy of CaZ+ antagonists has been reported to be less in SHR vessels than WKY rat vessels, which coincides with the above mentioned contradictory results reported in the Ca2+ permeability.…”

Calcium antagonists inhibit elevated potassium efflux from aorta of aldosterone-salt hypertensive rats.

“…Actions on sites other than POC require much higher concentrations. 36 -38 Although inhibitory effects of a dihydropyridine were observed on chemically skinned aorta from spontaneously hypertensive rats, 39 contributions from residual POC may not have been eliminated. McMahon and Paul 40 had to modify the skinning procedure significantly to overcome this problem for studies of rat aorta.…”

[Ca2+]i‐sensitive, IP3‐independent Ca2+ influx in smooth muscle of rat vas deferens revealed by procaine

“…It is possible that the method used in this study is not sensitive enough to detect a nifedipine-sensitive Ca2+ influx which may then act as a trigger for Ca2'-induced Ca2+ release from the sarcoplasmic reticulum, as has been suggested previously (Itoh et al, 1986). It is also possible that nifedipine inhibits the contraction of vas deferens to NA through mechanisms other than the blockade of calcium channels (Rinaldi et al, 1987;Jaquemond & Rougier, 1988;Xuan et al, 1989). However, the present observation that NA increases 45Ca influx in vasa deferentia that were preincubated with procaine and that this increased Ca2+ influx was blocked by nifedipine indicates that NA is capable of activating Ca2+ influx in this tissue through dihydropyridinesensitive calcium channels.…”