A study of the pharmacological reactivity of aortae from spontaneously hypertensive rats

Abstract

Increased vascular reactivity to pressor agents has often been observed in hypertensive states. A widely accepted hypothesis for this phenomenon attributes the reactivity changes to structural changes, such as vascular smooth muscle hypertrophy, that are thought to take place subsequent to the onset of hypertension. The work presented here studied vascular reactivity in an animal model of essential hypertension and offers an alternative explanation for this phenomenon. -- Spontaneously hypertensive rats (SHR) treated from conception with timolol, a β-adrenergic blocker, did hot develop high blood pressure. Thoracic aorta from these normotensive SHR exhibited increased reactivity to raised extracellular K⁺, when compared with tissues from timolol-treated Kyoto Wistar control rats. The normotensive SHR aorta also showed significant responsiveness to La³⁺ and to high extracellular Ca²⁺ concentrations without previously depolarizing the tissue with high K⁺. The response to La³⁺ was shown to be primarily mediated through a precipitation of the buffer in normal Krebs solution, resulting in a decrease in the pH of the bathing media. A large contractile response was recorded when these conditions were mimicked by the addition of HC1 to the Krebs solution bathing the SHR aorta. -- These observations indicate that altered reactivity in SHR aorta is not a consequence of hypertension. Reactivity changes were attributed to a deficient control of Ca²⁺ homeostasis in this tissue, which may prove to be a causative factor in the etiology of hypertension in the SHR.