Calcium handling by vascular myocytes in hypertension
Tostes, R.C.; Wilde, D.W.; Bendhack, L.M.; Webb, R.C.
Brazilian Journal of Medical and Biological Research 30(3): 315-323
1997
ISSN/ISBN: 0100-879X PMID: 9246229 Document Number: 477279
Calcium ions (Ca-2+) trigger the contraction of vascular myocytes and the level of free intracellular Ca-2+ within the myocyte is precisely regulated by sequestration and extrusion mechanisms. Extensive evidence indicates that a defect in the regulation of intracellular Call 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 Ca-2+ and intracellular Ca-2+ levels are elevated in aortic smooth muscle cells of SHR. We hypothesize that these changes are due to an increase in membrane Ca-2+ 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 Ca-2+ channel activity in hypertension; 2) Ca-2+ 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 Ca-2+ concentration is abnormally increased in vascular myocytes from hypertensive animals following treatment with Ca-2+ channel agonists and depolarizing interventions, and 4) using the voltage-clamp technique, the inward Call 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 Ca-2+ channel function and/or an increase in Ca-2+ channel density, resulting from increased channel synthesis or reduced turnover, underlies the increased vascular reactivity characteristic of hypertension.