Enhanced Depressor Response to Nitric Oxide in the Rostral Ventrolateral Medulla of Spontaneously Hypertensive Rats

Abstract

Abstract —Possible impairment of the l -arginine–nitric oxide (NO) pathway in the rostral ventrolateral medulla of adult spontaneously hypertensive rats (SHR) was investigated by microinjecting N G -nitro- l -arginine methyl ester (L-NAME), NOC 18 (an NO donor), or l -arginine. Unilateral injection of L-NAME (10 nmol/50 nL) into the rostral ventrolateral medulla significantly increased mean arterial pressure (MAP) in both SHR and Wistar-Kyoto rats (WKY). The increases in MAP did not differ significantly between the two strains (15±3 versus 10±2 mm Hg, respectively; n=8). In contrast, microinjection of l- arginine elicited significant ( P <.05) dose-dependent decreases in MAP in both strains, and these depressor responses were significantly greater in SHR than in WKY (in 10 nmol of l- arginine: –29±2 versus –15±2 mm Hg, respectively; n=8, P <.01). Similarly, microinjection of NOC 18 (10 nmol/50 nL) reduced MAP in both strains, and the depressor response was also significantly greater in SHR than in WKY (–38±7 versus –22±3 mm Hg, respectively; n=8, P <.05). These results suggest that the l -arginine–NO pathway in the rostral ventrolateral medulla is impaired in SHR and that this impairment may contribute to the increase in arterial pressure in this animal model of genetic hypertension.