Peripheral vascular resistance becomes elevated with age increasing the risk of cardiovascular disease. The physiologic changes in the vasculature that accompany aging closely resemble those seen in younger individuals with essential hypertension. The etiology of this condition may involve a defect in intracellular Ca2+ metabolism. We investigated this hypothesis in a rat model for hypertension using freshly-isolated arterial smooth muscle cells (SMC) which retain their in vivo phenotype. Mean systolic blood pressure showed a significant elevation between 6 and 30 months of age (131 mm vs 155 mm; p less than .001). Old SMC showed transiently higher resting intracellular Ca2+ levels compared to young cells following exposure to different extracellular Ca2+ loads. Blockade of T-type Ca2+ channels by Ni+ was more effective in lowering resting Ca2+ in young than in old SMC, whereas no age difference was found with respect to Ca2+ sequestration by sarcoplasmic reticulum (SR). Stimulation of SMC with the beta-agonist isoproterenol caused the redistribution of Ca2+ from the SR to the extracellular compartment. Measurements of the rate of isoproterenol-dependent Ca2+ removal from the SR showed that SMC from old rats retain significant levels of Ca2+ over longer periods of time than young SMC. Increased SR Ca2+ stores following beta-agonist stimulation could result in diminished smooth muscle relaxation and increased vascular tonus contributing to the development of hypertension in older animals.
