Calcium handling by vascular myocytes in hypertension

Calcium ions (Ca²⁺) trigger the contraction of vascular myocytes and the level of free intracellular Ca²⁺ within the myocyte is precisely regulated by sequestration and extrusion mechanisms. Extensive evidence indicates that a defect in the regulation of intracellular Ca²⁺ plays a role in the augmented vascular reactivity characteristic of clinical and experimental hypertension. For example, arteries from spontaneously hypertensive rats (SHR) have an increased contractile sensitivity to extracellular Ca²⁺ and intracellular Ca²⁺ levels are elevated in aortic smooth muscle cells of SHR. We hypothesize that these changes are due to an increase in membrane Ca²⁺ channel density and possibly function in vascular myocytes from hypertensive animals. Several observations using various experimental approaches support this hypothesis: 1) the contractile activity in response to depolarizing stimuli is increased in arteries from hypertensive animals demonstrating increased voltage-dependent Ca²⁺ channel activity in hypertension; 2) Ca²⁺ channel agonists such as Bay K 8644 produce contractions in isolated arterial segments from hypertensive rats and minimal contraction in those from normotensive rats; 3) intracellular Ca²⁺ concentration is abnormally increased in vascular myocytes from hypertensive animals following treatment with Ca²⁺ channel agonists and depolarizing interventions, and 4) using the voltage-clamp technique, the inward Ca²⁺ current in arterial myocytes from hypertensive rats is nearly twice as large as that from myocytes of normotensive rats. We suggest that an alteration in Ca²⁺ channel function and/or an increase in Ca²⁺ channel density, resulting from increased channel synthesis or reduced turnover, underlies the increased vascular reactivity characteristic of hypertension.