INCREASED NITRIC-OXIDE ACTIVITY IN EARLY RENOVASCULAR HYPERTENSION

A decreased influence of nitric oxide (NO) in the peripheral vasculatu re is associated with the pathophysiology of established hypertension, and some studies suggest that increased blood pressure positively cor relates with decreased NO production. If so, then the increased arteri al pressure in one-kidney, one-clip (1K1C) hypertensive rats should be associated with decreased circulating levels of nitrite/nitrate (NO2/ NO3; stable metabolites of NO) and guanosine 3',5'-cyclic monophosphat e (cGMP; mediator of NO action). We measured serum NO2/NO3 and cGMP le vels in early hypertensive 1K1C (2 wk after clipping) and sham-operate d one-kidney (1K) normotensive rats, treated orally with or without th e NO-synthase inhibitor N-G-nitro-L-arginine methyl ester (L-NAME, 2 w k). Compared with those in 1K rats, NO2/NO3 and cGMP levels were incre ased in 1K1C hypertensive rats but not in 1K1C rats treated with L-NAM E. NO2/NO3 and cGMP levels in L-NAME-treated 1K and 1K1C rats were sim ilar. Compared with that in 1K rats, systolic blood pressure (SBP) was increased in 1K1C rats and in L-NAME-treated 1K and 1K1C rats. The SB P increase in L-NAME-treated 1K1C rats was more rapid than in untreate d 1K1C rats. In early hypertension, increases in SBP positively correl ated with increases in serum NO2/NO3 and cGMP. After 2 wk of hypertens ion, circulating NO2/NO3 levels gradually declined and reached prehype rtension levels by the fifth week of hypertension. These results provi de evidence for increased NO synthesis in early hypertensive 1K1C rats , and this increased NO could be a compensatory mechanism to slow the development of hypertension in these animals.