Endothelium-derived relaxing factor responses in Doca-salt hypertensive rats

This study examined the contribution of endothelium-derived relaxing factor (EDRF) to the susceptibility of uninephrectomized rats to deoxycorticosterone acetate (DOCA)-salt hypertension. N omega-nitro-L-arginine, a probe for EDRF, produced smaller increases (P < 0.001) in mean arterial pressures in anesthetized hypertensive DOCA-salt rats than in sham rats. Acute L-arginine administration (300 mg/kg body wt i.v.) failed to reduce pressure in anesthetized DOCA-salt rats. Chronic oral and intraperitoneal L-arginine did not lower pressure in conscious DOCA-salt rats with established hypertension, nor did it prevent hypertension when begun in prehypertensive DOCA-salt rats. Preconstricted aortic rings from DOCA-salt rats had attenuated relaxation to acetylcholine compared with sham rats. Rings L-arginine-treated DOCA-salt rats had responses similar to DOCA-salt rats. Relaxation to nitroprusside was not different between any rat group. Thus EDRF is attenuated in DOCA-salt hypertension. However, unlike several other hypertensive models, the blunted EDRF response cannot be overcome by provision of L-arginine. These data suggest synthesis or release of EDRF may be noncompetitively inhibited in DOCA-salt hypertension.