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 spontaneously hypertensive rats (SHRs). 2. A slow intravenous infusion of NG-nitro-L-arginine methyl ester (L-NAME) (3 mg kg-1 h-1) did not produce any significant change in the mean arterial pressure during infusion. After stopping infusion of L-NAME, a slowly developing increase of the mean arterial pressure was observed during the following 40 min. 3. The pressor response to physostigmine (20, 40 and 80 micrograms 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 pressor responses to physostigmine, if physostigmine was injected after the end of a 1-hr infusion. 5. Acute pretreatment with increasing doses of physostigmine markedly affected the blood pressure response to L-arginine (i.e., L-arginine-caused hypotension was more pronounced), but only slightly that to L-NAME. 6. In conclusion, L-arginine, as a donor of NO, produced hypotension by itself and also decreased, but not significantly, the central cholinergically-mediated hypertension (CCMH) produced by physostigmine. It is quite possible that the peripheral NO released by L-arginine antagonized the increased adrenergic activity in the CCMH. This does happen in normotensive rats, but to a lesser degree than in SHRs, as shown in the current experiments. 7. Also, our results show that inhibition of endogenous NO biosynthesis using L-NAME does not necessarily lead to pressor response in vivo, at least in SHRs. It is concluded that L-arginine-nitric oxide pathways operate in SHRs, as well as in normotensive Wistar rats, but their role in modulating cholinergically-mediated regulation of the mean arterial pressure is less pronounced in SHRs than in normotensive animals.
Prostran
M S
MS
Department of Pharmacology, Faculty of Medicine, Belgrade, Yugoslavia.
Todorović
Z
Z
Varagić
V M
VM
D000818:Animals; D001120:Arginine / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects*; D002800:Cholinesterase Inhibitors / Q000494:pharmacology*; D004347:Drug Interactions; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006973:Hypertension / Q000503:physiopathology*; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D010830:Physostigmine / Q000494:pharmacology*; D051381:Rats; D011918:Rats, Inbred SHR
D002800:Cholinesterase Inhibitors; D004791:Enzyme Inhibitors; D009569:Nitric Oxide; D001120:Arginine; D010830:Physostigmine; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester