Calcium and increased vascular reactivity in hypertension.

Abstract

Enhanced vascular reactivity in hypertension has been associated with a number of changes in cellular calcium handling. These studies examined potential-operated calcium channel function in hypertension and possible mechanisms that may underlie enhanced vascular sensitivity to catecholamines in this disorder. Contractile responses to the potential-operated calcium channel agonist, Bay K 8644, were markedly increased in thoracic aortic strips from coarctation-hypertensive rats as compared to those from normotensive sham rats. This effect was related to elevated arterial pressure since it was not seen in abdominal aortae from hypertensive rats, a vessel that is protected from increased pressure. The role of pressure per se was supported by findings of increased sensitivity to Bay K 8644 in abdominal aortae from 2 kidney 1 clip hypertensive rats. In this comparable model of hypertension, the abdominal aorta is exposed to elevated blood pressure. To evaluate channel function within the microvasculature, intracellular calcium concentration (Ca$\sp{2+}$) $\sb{\rm i}$ was measured in rat pancreatic arterioles (15-35 $\mu$m diameter) using microspectrofluorimetry of fura-2. In these vessels, KCl-induced increases in (Ca$\sp{2+}$) $\sb{\rm i}$ were inhibited by nifedipine, consistent with activation of potential-operated calcium channels. Bay K 8644 evoked an increase in (Ca$\sp{2+}$) $\sb{\rm i}$ in approximately 25% of arterioles tested from both genetically hypertensive and normotensive control rats. Neither basal (Ca$\sp{2+}$) $\sb{\rm i}$ nor the change in (Ca$\sp{2+}$) $\sb{\rm i}$ produced by Bay K 8644 differed between the two strains. However, since arterioles of this size are distal to the major resistance vessels, they may be protected from pressure-induced damage seen in larger arteries. Mechanisms that may account for enhanced vascular sensitivity to norepinephrine in mesenteric arteries from DOCA hypertensive rats were also examined. Agonist affinity and the calcium sensitivity of the contractile elements were not altered in these vessels, but norepinephrine-stimulated $\sp{45}$Ca$\sp{2+}$ was increased, implicating a change in post receptor signal transduction involving calcium release from intracellular stores. In conclusion, these studies suggest that pressure-induced changes in potential-operated calcium channel function and augmented mobilization of intracellular calcium stores contribute to enhanced vascular reactivity in hypertension.