MODULATION OF VASCULAR CALCIUM-CHANNEL ACTIVITY IN RESPONSE TO ACUTE VOLUME EXPANSION IN RATS

The mechanisms of the increased resistance in hypertension are still u nclear. Several studies have indicated that the potential-sensitive Ca 2+ channels(PSC) are altered in arteries isolated from hypertensive pa tients or animals. An expansion of body fluid volume may trigger local autoregulatory responses or may induce the release of humoral factors , either of which could increase systemic vascular resistance and caus e volume-dependent forms of hypertension. We tested the hypothesis tha t volume expansion per se may cause the alterations of PSC similar to those seen in hypertension. For this, we examined the alterations of P SC in aortas from volume-expanded rats with the use of dihydropyridine -type Ca2+ channel activator, BayK 8644, in parallel with the changes in endothelium-dependent relaxation. Volume expansion was produced by a rapid intravenous infusion of saline(10 % of body weight) over 30 mi n in rats. At the end of infusion, rats were killed and aorta removed for in vitro measurement of isometric tension. Relaxation to acetylcho line(10(-7)-10(-5) mol\L, % relaxation to 10(-7) mmol/L. norepinephrin e contraction) was not significantly chnged. In contrast, contractile response to BayK 8644(10(-9)-10(-6) mol/L, % response to 50 mmol/L KCl ) was significantly enhanced in rats with volume expansion(12 control rats: 11.6+/-4.9%; 18 volume-expanded rats: 40.9+/-10.4% at 10(-6) mol /L, p<0.05). These findings suggest that acute volume expansion could induce a similar enhanced vascular Ca2+ channel activity to that seen in hypertension in rats.