Elevated vascular reactivity in the timolol-treated spontaneously hypertensive rat

Abstract

Spontaneously hypertensive rats (SHR) treated in utero with a low dose, and from weaning with 6 mg/kg per day of oral timolol, a noncardioselective β-adrenergic blocker, did not develop hypertension. Isolated aortic rings from these animals showed increased reactivity to raised extracellular K⁺, when compared with tissues from timolol-treated Kyoto-Wistar (WKY) control rats. The normotensive SHR aorta also showed significant responsiveness to H⁺ and to high Ca²⁺ concentrations without previously depolarizing the tissue with high K⁺ These observations suggest that the increased reactivity seen in vascular smooth muscle from this animal does not develop secondary to elevated peripheral resistance and subsequent hypertrophy, and that the initiation of hypertension in this animal may be related to a membrane defect and (or) cellular defect which results in a facilitation of Ca²⁺ availability for the contractile proteins of the SHR vascular smooth muscle cell.