Impaired nitric oxide-independent dilation of renal afferent arterioles inspontaneously hypertensive rats

Sustained hypertension alters vasomotor regulation in various vascular beds . We studied whether nitric oxide (NO)-dependent and NO-independent vasodil ator mechanisms are altered in renal microvessels in hypertension. To direc tly visualize the renal microcirculation, the isolated perfused hydronephro tic rat kidney model was used. After pretreatment with indomethacin (100 mu mol/l), afferent arterioles were constricted by norepinephrine (NE) or by increasing renal arterial pressure (i.e., myogenic constriction; from 80 to 180 mmHg). Acetylcholine (ACH) was then added, and the renal microvascular response was assessed by computer-assisted video image analysis. A similar protocol was conducted in the presence of nitro-L-arginine methylester (L- NAME; 100 mu mol/l). During NE constriction, ACH caused dose-dependent and sustained vasodilation of the afferent arteriole, similar in magnitude in W istar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR). In the pr esence of L-NAME, ACH (0.01-1 mu mol/l) elicited only transient dilation, a nd the degree of vasodilation was very low in SHR. During myogenic constric tion, afferent arterioles from WKY and SHR kidneys responded to ACH with on ly transient vasodilation, which was unaffected by NO inhibition; the trans ient vasodilative responses elicited by ACH (0.1-1 mu mol/l) were smaller i n SHR than in WKY. In conclusion, ACH has both sustained and transient vaso dilative effects on the afferent arteriole. Sustained vasodilation is attri buted to NO generation, which is similar in WKY and SHR. In contrast, trans ient vasodilation, mediated by NO-independent vasodilator factors, is impai red in SHR. Deranged vasodilatory mechanisms in hypertension may disturb th e renal microcirculation, which may result in renal injury.