Altered Calcium Handling in Peripheral Nerve Terminals and Blood Vessels in Spontaneously Hypertensive Rats

Abstract

The present study was designed to clarify the roles of N-type and P/Q-type calcium channels in the increased sympathetic activity of spontaneously hypertensive rats (SHR/Izm). We also tested in SHR/Izm the contribution to increased vascular tone of α 1A adrenoceptor-linked L-type calcium channels and α 1B receptor-mediated calcium mobilization from the sarcoplasmic reticulum. Methods: Six-week-old SHR/Izm and Wistar-Kyoto rats (WKY/Izm) were used. A superior mesenteric arterial preparation was electrically stimulated before and after treatment with ω -conotoxin GVIa (N-type calcium channel blocker [CgTX]) and ω -agatoxinIVa (P/Q-type calcium channel blocker [AgaTX]). Pressor response to norepinephrine was measured before and after treatment with the α 1A blocker WB-4101 and the α 1B blocker chloroethyl clonidine (CEC). To determine the intracellular calcium store size, the effects of ryanodine on pressor response and caffeine-induced vascular contraction were also tested. Results: Norepinephrine overflow evoked by electrical stimulation was increased in SHR/Izm. CgTX but not AgaTX suppressed the increased NE overflow in SHR/Izm. WB-4101 suppressed the pressor response to norepinephrine in SHR/Izm but not WKY/Izm rats. CEC had no effects on pressor response to norepinephrine in both types of rats. Caffeine-induced contraction to a high potassium-induced maximal contraction ratio was reduced in SHR/Izm. The effect of ryanodine on pressor response was reduced in SHR/Izm. Conclusion: N-type calcium channels but not P/Q-type calcium channels play an important role in the increased sympathetic tone in SHR/ Izm. Although α 1A adrenoceptor-linked L-type calcium channels contribute to the increased vascular tone, the intracellular calcium store size was reduced in SHR/Izm.