PHYSOSTIGMINE AND MODULATORS OF NITRIC-OXIDE SYSTEM ON THE MEAN ARTERIAL-PRESSURE OF THE SPONTANEOUSLY HYPERTENSIVE RAT

1. A slow intravenous infusion of L-arginine (3 mg kg(-1)) lasting one hr produced significant hypotension in urethane-anaesthetized spontan eously hypertensive rats (SHRs). 2. A slow intravenous infusion of N-G -nitro-L-arginine methyl ester (L-NAME) (3 mg kg(-1) h(-1)) did not pr oduce any significant change in the mean arterial pressure during infu sion. After stopping infusion of L-NAME, a slowly developing increase of the mean arterial pressure was observed during the following 40 min , 3. The presser response to physostigmine (20, 40 and 80 mu g kg(-1), IV), injected during a slow intravenous infusion of either L-arginine or L-NAME, was not changed. 4. L-arginine and L-NAME depressed the pr esser responses to physostigmine, if physostigmine was injected after the end of a I hr infusion. 5. Acute pretreatment with increasing dose s of physostigmine markedly affected the blood pressure response to L- arginine (i.e., L-arginine-caused hypotension was more pronounced), bu t only slightly that to L-NAME. 6. In conclusion, L-arginine, as a don or of NO, produced hypotension by itself and also decreased, but not s ignificantly, the central cholinergically mediated hypertension (CCMH) produced by physostigmine. It is quite possible that the peripheral N O released by L-arginine antagonized the increased adrenergic activity in the CCMH. This does happen in normotensive rats, but to a lesser d egree than in SHRs, as shown in the current experiments. 7. Also, our results show that inhibition of endogenous NO biosynthesis using L-NAM E does not necessarily lead to presser response in vivo, at least in S HRs. It is concluded that L-arginine nitric oxide pathways operate in SHRs, as well as in normotensive Wistar rats, but their role in modula ting cholinergically mediated regulation of the mean arterial pressure is less pronounced in SHRs than in normotensive animals. Copyright (C ) 1997 Elsevier Science Inc.