Effect of nitro-L-arginine on electrical and mechanical responses to acetylcholine in the superior mesenteric artery from stroke-prone hypertensive rat

Citation
P. Ghisdal et al., Effect of nitro-L-arginine on electrical and mechanical responses to acetylcholine in the superior mesenteric artery from stroke-prone hypertensive rat, BR J PHARM, 128(7), 1999, pp. 1513-1523
Citations number
53
Categorie Soggetti
Pharmacology & Toxicology
Journal title
BRITISH JOURNAL OF PHARMACOLOGY
ISSN journal
00071188 → ACNP
Volume
128
Issue
7
Year of publication
1999
Pages
1513 - 1523
Database
ISI
SICI code
0007-1188(199912)128:7<1513:EONOEA>2.0.ZU;2-E
Abstract
1 High salt diet is known to aggravate the vascular pathology in spontaneou sly hypertensive stroke-prone rats (SHR-SP). The aim of the present study w as to assess the involvement of endothelial dysfunction in this effect. Con tractile tension and membrane potential were simultaneously recorded in sup erior mesenteric artery rings of untreated and NaCl-loaded (1% NaCl in the drinking water) SHR-SP and normotensive Wistar Kyoto rats (WKY). 2 In unstimulated artery, hyperpolarization evoked by acotylcholine was not different in WKY and in NaCl-loaded WKY; it was reduced in SHR-SP and furt her reduced in NaCl-loaded SHR-SP. Hyperpolarization was unaffected by N-om ega-nitro-L-arginine (L-NA) but was abolished in high-KCl solution. 3 In noradrenaline-stimulated artery, ACh-evoked hyperpolarization and rela xation were not different in WKY and in SHR-SP. NaCl-treatment did not affe ct the responses to ACh in WKY but decreased maximum relaxation in SHR-SP f rom 93 +/- 2% to 72 +/- 7% of the contraction. In WKY, in NaCl-loaded WKY a nd in SHR-SP, L-NA similarly shifted the concentration-relaxation curve to ACh to the right and depressed its maximum but L-NA did not affect the hype rpolarization to ACh. In NaCl-loaded SHR-SP, L-NA blunted the effects of AC h on membrane potential and on contraction. 4 The NO donor SNAP abolished the depolarization and the contraction evoked by noradrenaline with the same potency in WKY and in untreated SHR-SP but was more potent in NaCl-loaded SHR-SP. 5 In KCl-contracted arteries the relaxations to ACh were not different in W KY and SHR-SP but NaCl-loaded SHR-SP were more sensitive to ACh. 6 The results showed that NaCl-rich diet markedly reduced the L-NA-resistan t responses to ACh and increased the sensitivity to NO in SHR-SP.