Ion channels in vascular smooth muscle: alterations in essential hypertension.
Essential hypertension is characterized by a near normal cardiac output but an increase in total peripheral resistance. In turn, total peripheral resistance is controlled directly by the diameter of the small arteries and arterioles like those in the kidney. The dynamic regulation 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 and maintain the contractile state of the vascular smooth muscle cells in hypertension and the potential prevention of hypertension through gene therapy. These specific channels include Ca2+, K(Ca), Kv, and Cl- channels. In hypertension, it has been reported that increased activity of Ca2+ channels and decreased activity of Kv channels are responsible for the increased contractile tone and resting membrane potential observed in dissociated vascular smooth muscle cells from the spontaneously hypertensive rat. In contrast, increased activity of K(Ca) channels in vascular smooth muscle cells of the SHR has been hypothesized to dampen or brake the activity of Ca2+ and Kv channels. Finally, recent evidence suggests that introducing angiotensin II type-1 receptor antisense into prehypertensive rat pups prevents the onset of pathophysiological alterations observed in hypertension including K+ channel alterations. These results suggest that gene therapy may be a useful pharmacological and physiological tool to combat hypertension.
Martens
J R
JR
Department of Physiology, University of Florida, Gainesville 32610, USA.
Gelband
C H
CH
D000818:Animals; D015220:Calcium Channels / Q000502:physiology; D018118:Chloride Channels / Q000502:physiology; D006801:Humans; D006973:Hypertension / Q000503:physiopathology*; D007473:Ion Channels / Q000502:physiology*; D009131:Muscle, Smooth, Vascular / Q000502:physiology*; D015221:Potassium Channels / Q000502:physiology
D015220:Calcium Channels; D018118:Chloride Channels; D007473:Ion Channels; D015221:Potassium Channels