Effects of chloride substitution in isolated mesenteric blood vessels from Dahl normotensive and hypertensive rats.
The purpose of this investigation was to examine the effect of Cl-free medium, nitric oxide synthase inhibitor (N nitro-L-arginine methyl ester; L-NAME), and Cl channel antagonist (niflumic acid), on alpha1-adrenoceptor (cirazoline) mediated responses in the isolated mesenteric blood vessels from Dahl salt-resistant normotensive (SRN) and salt-sensitive hypertensive (SSH) rats on a 4% salt diet for 7 weeks. Cirazoline produced dose-dependent vasoconstriction in blood vessels of SRN and SSH rats. Replacement of extracellular Cl with propionate ions significantly inhibited (P < 0.05) cirazoline-mediated vasoconstriction in SRN but not in SSH rats. Perfusion with L-NAME (10 microM) augmented responses to cirazoline in SRN but not in SSH rats. In Cl-free medium, addition of L-NAME had a biphasic effect on cirazoline responses; potentiation of responses at the lower doses and attenuation at the highest dose. Niflumic acid (10 microM) significantly inhibited cirazoline responses with the inhibition being more pronounced in SRN than SSH rats. The resting Em of smooth muscle cells was -68.0 +/- 4.2 mV (mean +/- SD; n = 87) and -67.2 +/- 4.8 mV (n = 88), in SRN and SSH rats, respectively. Perfusion with Cl-free medium produced a significant depolarization that was larger in smooth muscle cells of SSH (-57.4 +/- 4.8 mV, n = 38) than SRN (-61.3 +/- 5.4 mV, n = 35) rats, while L-NAME depolarized the smooth muscle cells of SRN (-62.1 +/- 6.5 mV, n = 36) but not SSH (-67.5 +/- 4.2 mV, n = 34) rats. The data supports the view that Cl handling and Ca-dependent Cl channels seem to undergo modification as a consequence of salt-induced hypertension. It is also possible that the modified role of nitric oxide on membrane potential may have a direct bearing on the changes observed in Cl handling in blood vessels of SRN versus SSH rats.
Parai
Kakoli
K
Division of Basic Medical Sciences, Faculty of Medicine, Memorial University of Newfoundland, St. John's, NL, Canada.
Tabrizchi
Reza
R
D000818:Animals; D002712:Chlorides / Q000494:pharmacology; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006973:Hypertension / Q000503:physiopathology*; D007093:Imidazoles / Q000494:pharmacology; D066298:In Vitro Techniques; D007552:Isotonic Solutions / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects; D008638:Mesenteric Arteries / Q000187:drug effects / Q000503:physiopathology*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009544:Niflumic Acid / Q000494:pharmacology; D009566:Nitrates / Q000097:blood; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D009573:Nitrites / Q000097:blood; D051381:Rats; D020303:Rats, Inbred Dahl; D017673:Sodium Chloride, Dietary / Q000008:administration & dosage / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000494:pharmacology
D002712:Chlorides; D016861:Cyclooxygenase Inhibitors; D004791:Enzyme Inhibitors; D007093:Imidazoles; D007552:Isotonic Solutions; C051865:Krebs-Ringer solution; D009566:Nitrates; D009573:Nitrites; D017673:Sodium Chloride, Dietary; D014662:Vasoconstrictor Agents; D009544:Niflumic Acid; D019001:Nitric Oxide Synthase; C014282:cirazoline; D019331:NG-Nitroarginine Methyl Ester