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CARDIOVASCULAR

Acute and Chronic Captopril, but Not Prazosin or Nifedipine, Normalize Alterations in Adrenergic Intracellular Ca²⁺ Handling Observed in the Mesenteric Arterial Tree of Spontaneously Hypertensive Rats

Departament de Farmacologia, Facultat de Farmàcia, Universitat de València, València, Spain (R.M., R.G., E.S., E.A., M.A.N., M.D.I., M.P.D.); and Departamento de Farmacología, Facultad de Medicina, Universidad Complutense de Madrid, Madrid, Spain (F.P.-V.)

The effect of hypertension and acute (36-h) or chronic (from age 6 to 16 weeks) antihypertensive treatment with prazosin (2 mg kg^-1 per day), nifedipine (50 mg kg^-1 per day), or captopril (50 mg kg^-1 per day) on Ca²⁺ mobilization due to ₁-adrenoceptor activation was analyzed in functional studies using arterial rings [four conductance/distributing vessels: aorta, main mesenteric, iliac, and tail arteries and two resistance vessels; first and second small mesenteric artery branches obtained from spontaneously hypertensive rats (SHR, 6 and 16 weeks old) and age-matched Wistar Kyoto rats (WKY)]. Maximal response to noradrenaline in the presence of extracellular Ca²⁺ is not affected by hypertension or by the antihypertensive treatment. The extracellular Ca²⁺-independent contractile responses increased with age in iliac, tail, and small mesenteric arteries (SMA) and were further increased in SHR in SMA from both young and adult animals and in the main mesenteric artery of adult SHR. In main mesenteric artery, this increased contraction in SHR was associated with a higher increase in cytosolic [Ca²⁺] mobilized by noradrenaline without changes in the total stored Ca²⁺. Acute or chronic treatment with captopril abolished the differences observed between WKY and SHR in the noradrenaline-induced contraction in mesenteric arteries loaded in Ca²⁺-free medium. In contrast, animals acutely treated with prazosin or chronically treated with either prazosin or nifedipine exhibit the same differences in Ca²⁺ handling than untreated rats. In conclusion, these differences are not a consequence of increased blood pressure but precede it and can only be normalized by inhibition of the rennin-angiotensin system.

Address correspondence to: Dr. Pilar D'Ocon, Departament de Farmacologia, Facultat de Farmàcia, Universitat de València, Avda Vicent Andrés Estelles s/n, Burjassot, 46100 València, Spain. E-mail: m.pilar.docon{at}uv.es