MECHANISM OF THE HYPERTENSION PRODUCED BY INHIBITION OF NITRIC-OXIDE BIOSYNTHESIS IN RATS

We have examined the effects of inhibition of nitric oxide (NO) biosynthesis on the blood pressure (BP) of anesthetized rats using N-nitro-L-arginine (NOLA). Infusion of NOLA (5, 15, or 60 mg/kg) caused a rise in BP of up to 155 mm Hg that could be prevented (but not reversed) by administration Of L-arginine (300 and 600 mg/kg, i.v.). In addition, NOLA (5-60 mg/kg) reduced the duration of the depressor response to acetylcholine (1-mu-g/kg), but not that of sodium nitroprusside (10-mu-g/kg). In rats treated with NOLA (15 mg/kg), infusion of the K+ channel antagonist glibenclamide (30 mg/kg) failed to inhibit the residual depressor response to acetylcholine, indicating that this response is not due to hyperpolarization of the vascular smooth muscle via activation of ATP-sensitive K+ channels. NOLA (5 or 15 mg/kg) still produced rises in BP in anesthetized rats treated with the angiotensin-converting enzyme inhibitor enalaprilat (5 mg/kg; rise of 62 +/- 6 mm Hg) and in pithed rats infused with norepinephrine (rise of 62 +/- 5 mm Hg). These data suggest that NOLA raises arterial pressure by a mechanism that is not dependent on the central nervous system nor on the renin-angiotensin system. Under resting conditions, the continuous production of NO in resistance vessels may play an important role in the regulation of peripheral vascular resistance.