Effects of diltiazem (a calcium antagonist) on neurosecretion and vascular responsiveness in hypertension

The purpose of the present study was to analyse the mechanisms of the vasodepressive action of diltiazem (one of the Ca antagonists) in hypertension. The perfused mesenteric preparation was used in spontaneously hypertensive rats (SHR, Okamoto and Aoki, 7-9 weeks old) and age-matched Wistar-Kyoto rats (WKY). The effects of diltiazem on norepinephrine overflow from the sympathetic nerve endings and vascular responsiveness were investigated. Pressor responses to electrical nerve stimulation were inhibited dose-dependently by diltiazem. Norepinephrine overflow during periarterial nerve stimulation was also inhibited by diltiazem, and its suppression was significantly greater in SHR than in the age-matched WKY rats. Vasoconstrictor responses to exogenous norepinephrine were also reduced by diltiazem in both SHR and WKY rats. The inhibitory effects of diltiazem were more evident in SHR than in WKY rats. These results demonstrate that diltiazem could affect both pre- and postsynaptic sites of the resistance vessels and cause a decrease in electrically stimulated norepinephrine overflow from the sympathetic nerve endings, in addition to the direct effects on the responsiveness of the vascular smooth muscles. The marked reduction of the pressor responses and norepinephrine overflow by diltiazem in SHR might explain the Ca-dependency in the pathogenesis of hypertension.