Neurotransmitter release, vascular responsiveness and their calcium-mediated regulation in perfused mesenteric preparation of spontaneously hypertensive rats and DOCA-salt hypertension.
To investigate the role of norepinephrine release from the sympathetic nerve endings and vascular responsiveness to endogenous and exogenous norepinephrine in the pathogenesis of hypertension, the perfused mesenteric preparations from spontaneously hypertensive rats (SHR) and DOCA-salt hypertension were used. In addition, the effects of two calcium antagonists on norepinephrine release by electrical stimulation and the vasoconstrictor responses to norepinephrine were examined to evaluate the calcium dependency of norepinephrine release and the vascular responsiveness in hypertension. The vascular responsiveness was increased in SHR and DOCA-salt hypertension in both early and later phases. Norepinephrine overflow from the sympathetic nerve terminals was enhanced only in young SHR and the chronic phase of DOCA-salt hypertension. After infusion of verapamil, a calcium antagonist, into the perfusate, the pressor responses and norepinephrine overflow by electrical stimulation were more inhibited in SHR, especially in young SHR, and the chronic phase of DOCA-salt hypertension than in controls. These results suggest that calcium dependency in both pre- and postsynaptic sites of neurotransmission may contribute to the pathogenesis of hypertension.
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D003900:Desoxycorticosterone / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D006973:Hypertension / Q000139:chemically induced* / Q000503:physiopathology; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects / Q000502:physiology*; D009638:Norepinephrine / Q000378:metabolism* / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR / Q000502:physiology*; D011919:Rats, Inbred Strains / Q000502:physiology*; D011921:Rats, Inbred WKY; D013997:Time Factors; D014700:Verapamil / Q000494:pharmacology
D003900:Desoxycorticosterone; D014700:Verapamil; D002118:Calcium; D009638:Norepinephrine