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Haemodynamic changes and acetylcholine‐induced hypotensive responses after N G ‐nitro‐ l ‐arginine methyl ester in rats and cats
Author(s) -
Gelderen E. Marcel,
Heiligers Jan P.C.,
Saxena Pramod R.
Publication year - 1991
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1991.tb12349.x
Subject(s) - cats , acetylcholine , hemodynamics , pharmacology , anesthesia , chemistry , medicine , endocrinology
1 The haemodynamic effects of N G ‐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 μg 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 (300 mg kg −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 (10–100 mg 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.