title: Effect of nitro-L-arginine on electrical and mechanical responses to acetylcholine in the superior mesenteric artery from stroke-prone hypertensive rat.
abstract: 1. High salt diet is known to aggravate the vascular pathology in spontaneously hypertensive stroke-prone rats (SHR-SP). The aim of the present study was to assess the involvement of endothelial dysfunction in this effect. Contractile tension and membrane potential were simultaneously recorded in superior 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 acetylcholine was not different in WKY and in NaCl-loaded WKY; it was reduced in SHR-SP and further reduced in NaCl-loaded SHR-SP. Hyperpolarization was unaffected by N(omega)-nitro-L-arginine (L-NA) but was abolished in high-KCl solution. 3. In noradrenaline-stimulated artery, ACh-evoked hyperpolarization and relaxation were not different in WKY and in SHR-SP. NaCl-treatment did not affect the responses to ACh in WKY but decreased maximum relaxation in SHR-SP from 93+/-2% to 72+/-7% of the contraction. In WKY, in NaCl-loaded WKY and 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 hyperpolarization to ACh. In NaCl-loaded SHR-SP, L-NA blunted the effects of ACh 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 WKY 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-resistant responses to ACh and increased the sensitivity to NO in SHR-SP.
authors.affiliation: Laboratoire de Pharmacologie, Université Catholique de Louvain, UCL 5410, Avenue Hippocrate, 54-B 1200 Bruxelles, Belgium.
authors.forename: P
authors.initials: P
authors.lastname: Ghisdal
authors.forename: T
authors.initials: T
authors.lastname: Godfraind
authors.forename: N
authors.initials: N
authors.lastname: Morel
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology*; D000818:Animals; D004338:Drug Combinations; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D017538:Mesenteric Artery, Superior / Q000187:drug effects* / Q000502:physiology; D009119:Muscle Contraction / Q000187:drug effects; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D020030:Nitric Oxide Donors / Q000494:pharmacology; D019335:Nitroarginine / Q000494:pharmacology*; D009638:Norepinephrine / Q000494:pharmacology; D010396:Penicillamine / Q000031:analogs & derivatives / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology*
chemical_list: D004338:Drug Combinations; D004791:Enzyme Inhibitors; D020030:Nitric Oxide Donors; C110881:S-nitro-N-acetylpenicillamine; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D019335:Nitroarginine; D011189:Potassium Chloride; D010396:Penicillamine; D000109:Acetylcholine; D019331:NG-Nitroarginine Methyl Ester; D009638:Norepinephrine