Older individuals demonstrate an increased incidence of hypertension as wel as a diminished response to beta-adrenergic receptor agonists which mediate vascular smooth muscle relaxation and systemic arterial compliance (vascula stiffness). The etiology of these conditions may involve common factors which affect intracellular ion metabolism and structural components of the vasculature. We have extended our investigations of vascular smooth muscle cell function in a rat model demonstrating age-related systolic hypertension. Freshly-isolated arterial smooth muscle cells (SMC) treated with isoproterenol (ISO) were able to redistribute Ca2+ from the sarcoplasmic reticulum (SR) to the extracellular space by a mechanism involving activation of the sarcolemmal Na+/K+ pump and Na+/Ca2+ exchanger. Old SMC had a significantly higher SR Ca2+ content compared to young cells following ISO exposure, whereas baseline SR and cytoplasmic Ca2+ levels wer unchanged. Aortic tissue slices from old animals showed reduced 86Rb+ uptak in the presence of ISO, indicating a diminished capacity for beta-activatio of the Na+/K+ pump. Western blots demonstrated reduced levels of the a1 isoform of Na+/K+-ATPase in rat tail artery homogenates. These results link the age-related increase in SR Ca2+ to a reduced level of stimulation of th sarcolemmal Na+/K+ pump by beta-agonists. In the presence of vasconstrictors, the increased SR Ca2+ stores following beta-stimulation ma contribute to diminished smooth muscle relaxation, increased arterial stiffness and systolic hypertension in older animals.
