Study of in vivo and in vitro resting vasodilator nitric oxide tone in normotensive and genetically hypertensive rats.
The effects of NG-nitro-L-arginine (L-NNA) on mean arterial pressure and the effects of both L-NNA and methylene blue on isolated aorta tone, were studied in order to elucidate potential alterations in vasodilator resting nitric oxide (NO) tone in genetic hypertension. L-NNA produced a significantly greater increase of mean arterial pressure in spontaneously hypertensive rats (SHR) than in Wistar Kyoto (WKY) rats; in both cases, L-arginine completely inhibited the L-NNA hypertensive effect. Neither ganglion blockade with hexamethonium nor cyclooxygenase inhibition with indomethacin significantly modified the effect of L-NNA in both rat strains. In intact aorta rings, after submaximally contraction with KCI (25 mM), both L-NNA and methylene blue induced strong dose-dependent contractions. The maximum contractions were, however, significantly greater in WKY rats than in SHR. The mechanical elimination of endothelium markedly inhibited both L-NNA and methylene blue maximum contractions. In intact rings, L-arginine completely inhibited the L-NNA effects in both rat strains; in rubbed rings, the L-arginine inhibitory effects were strong in WKY rats but not important and erratic in SHR. L-Arginine had no effect on the contractions induced only by KCI in any of the preparations. In WKY rat-rubbed rings, sodium nitroprusside was significantly more effective in relaxing the contractions in response to 25 mM KCI than the contractions in response to methylene blue. These results indicate that contractions induced by L-NNA and methylene blue in isolated aorta are principally due to the inhibition of an important endothelial resting vasodilator NO tone. They also show that hypertension reduces the resting vasodilator NO tone in isolated rat aorta, in spite of enhancing the total vasodilator NO tone in anaesthetized rat.
Gil-Longo
J
J
Departamento de Farmacoloxía, Facultade de Farmacia, Universidade de Santiago de Compostela, Spain.
Fernández-Grandal
D
D
Alvarez
M
M
Sieira
M
M
Orallo
F
F
D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000502:physiology; D001794:Blood Pressure / Q000187:drug effects; D018738:Hexamethonium / Q000494:pharmacology; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D008751:Methylene Blue / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology*; D010656:Phenylephrine / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D014655:Vascular Resistance / Q000502:physiology*; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology; D019323:omega-N-Methylarginine / Q000494:pharmacology
D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D010656:Phenylephrine; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D018738:Hexamethonium; D008751:Methylene Blue; D007213:Indomethacin