Haemodynamic changes and acetylcholine-induced hypotensive responses after NG-nitro-L-arginine methyl ester in rats and cats.
1. The haemodynamic effects of NG-nitro-L-arginine methylester (L-NAME; 1, 3, 10 and 30 mg kg-1) and its potential ability to attenuate the hypotensive responses to acetylcholine (0.03, 0.1, 1.0 and 3.0 micrograms kg-1) have been investigated in anaesthetized rats and cats. 2. In the rat, L-NAME elicited a dose-dependent pressor effect increasing mean arterial blood pressure from the baseline value of 116 +/- 4 mmHg to a maximum of 156 +/- 6 mmHg with 30 mg kg-1. This increase in blood pressure could be only partly reversed by L-arginine (300 mg kg-1). However, the increase in blood pressure by lower doses (up to 10 mg kg-1) of L-NAME was effectively reversed by L-arginine (1000 mg kg-1). 3. In the cat, L-NAME did not significantly modify systemic haemodynamic variables (heart rate, mean arterial blood pressure, cardiac output, stroke volume or total peripheral resistance), when compared to the changes in saline-treated animals. Administration of L-arginine did not cause any significant effect in cats treated with L-NAME, but some decrease in heart rate and increases in cardiac output and stroke volume were observed in the saline-treated group. 4. With the lowest dose (1 mg kg-1), L-NAME did not affect tissue blood flows in the cat, but higher doses (3 and 30 mg kg-1) significantly reduced blood flows to the mesentery, stomach, spleen, intestines, lungs and the total liver. L-Arginine (300mgkg-1) injected into the control (saline-treated) animals resulted in a significant increase in blood flow to the heart, mesentery, lungs as well as the total liver, particularly its portal fraction. L-Arginine-induced increases in tissue blood flows (mesentery, kidneys, spleen, lungs, total liver and portal blood flow) in saline-treated animals were attenuated in animals treated with L-NAME.5. The acetylcholine-induced peak hypotensive response was not reduced in rats or cats by L-NAME. The duration of acetylcholine response was, however, attenuated in both species by L-NAME. Treatment with L-arginine (10-100mg kg- 1) did not change the acetylcholine-induced hypotension.6. The above results reveal a marked difference between the haemodynamic effects of L-NAME in rats and cats and suggest that in cats, unlike rats, the role of the L-arginine-NO pathway in the regulation of blood pressure is rather limited, although such a pathway may exist in several tissues. Furthermore, the hypotensive response to acetylcholine in both species seems to be mediated largely by NO-independent pathways.
Marcel van Gelderen
E
E
Department of Pharmacology, Faculty of Medicine and Health Sciences, Erasmus University Rotterdam, The Netherlands.
Heiligers
J P
JP
Saxena
P R
PR
D000109:Acetylcholine / Q000494:pharmacology*; D000818:Animals; D001120:Arginine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D001783:Blood Flow Velocity; D001794:Blood Pressure / Q000187:drug effects*; D002408:Catheters, Indwelling; D002415:Cats; D005260:Female; D006439:Hemodynamics / Q000187:drug effects*; D008297:Male; D019335:Nitroarginine; D051381:Rats; D011919:Rats, Inbred Strains
D019335:Nitroarginine; D001120:Arginine; D000109:Acetylcholine