ION CHANNELS IN VASCULAR SMOOTH-MUSCLE - ALTERATIONS IN ESSENTIAL-HYPERTENSION

Essential hypertension is characterized by a near normal cardiac outpu t but an increase in total peripheral resistance. In turn, total perip heral resistance is controlled directly by the diameter of the small a rteries and arterioles like those in the kidney. The dynamic regulatio n of renal vessel diameter is governed by the contractile state of the vascular smooth muscle cells that line the vessel walls. This review addresses the role of a number of different ion channels to initiate a nd maintain the contractile state of the vascular smooth muscle cells in hypertension and the potential prevention of hypertension through g ene therapy. These specific channels include Ca2+, K-Ca, K-v, and Cl- channels. In hypertension, it has been reported that increased activit y of Ca2+ channels and decreased activity of K-v channels are responsi ble for the increased contractile tone and resting membrane potential observed in dissociated vascular smooth muscle cells from the spontane ously hypertensive rat. In contrast, increased activity of K-Ca channe ls in vascular smooth muscle cells of the SHR has been hypothesized to dampen or brake the activity of Ca2+ and K-v channels. Finally, recen t evidence suggests that introducing angiotensin II type-1 receptor an tisense into prehypertensive rat pups prevents the onset of pathophysi ological alterations observed in hypertension including K+ channel alt erations. These results suggest that gene therapy may be a useful phar macological and physiological tool to combat hypertension.