NITRIC-OXIDE MODULATES BUT DOES NOT IMPAIR MYOGENIC VASOCONSTRICTION OF THE AFFERENT ARTERIOLE IN SPONTANEOUSLY HYPERTENSIVE RATS - STUDIES IN THE ISOLATED-PERFUSED HYDRONEPHROTIC KIDNEY

Renal autoregulation curves are reset toward higher renal arterial pressure in spontaneously hypertensive rats (SHR) compared with those in Wistar-Kyoto rats (WKY). We previously demonstrated that myogenic afferent arteriolar constriction is shifted to higher renal arterial pressure. To investigate whether nitric oxide participates in the regulation of myogenic tone, we examined the effect of nitro-L-arginine on myogenic afferent arteriolar constriction in kidneys from SHR and WKY, using the isolated perfused hydronephrotic kidney. Elevating pressures from 40 to 80 mm Hg caused increases in afferent arteriolar diameter in WKY (from 18.2+/-0.4 to 19.0+/-0.3 mu m) and SHR (from 17.3+/-0.6 to 18.4+/-0.6 mu m). Further pressure elevation elicited constriction at 100 mm Hg in WKY (17.9+/-0.3 mu m), but significant constriction was observed at 120 mm Hg in SHR (17.3+/-0.6 mu m), indicating a resetting in myogenic responses to higher pressures. In WKY, after treatment with 10 mu mol/L nitro-L-arginine, afferent arterioles exhibited pressure-dependent constriction, with a threshold pressure for constriction at 80 mm Hg. The addition of 100 mu mol/L nitro-L-arginine had no further effect on myogenic responsiveness in WKY. In contrast, in SHR, nitro-L-arginine dose-dependently shifted the myogenic responses toward lower renal arterial pressure, with threshold pressures for constriction observed at 100 mm Hg (10 mu mol/L) and 80 mm Hg (100 mu mol/L). Finally, in the presence of 100 mu mol/L nitro-L-arginine, afferent arterioles manifested 24+/-3% and 20+/-2% constriction at 180 mm Hg in WKY and SHR, respectively, not different from those in the absence of nitro-L-arginine (WKY, 21+/-1%; SI-IR, 19+/-2%). In conclusion, the present study demonstrates that nitric oxide modulates but does not impair myogenic afferent arteriolar contractility. Furthermore, elimination of the resetting in afferent arteriolar response by nitric oxide blockade suggests an augmented effect of nitric oxide on this vessel in SHR. The enhanced nitric oxide effect on afferent arterioles from SHR kidneys may account for the adaptive mechanisms of renal microvessels to hypertension.