[Effect of angiotensin II and alpha2 adrenergic receptor antagonists on angiotensin II-stimulated nitric oxide release].
The aim of the present work was to characterize the interaction between the adrenergic system and angiotensin II-stimulated nitric oxide (NO) release in rabbit aorta. Rings of thoracic aorta were placed in an isolated organ bath. Equilibration was performed during 30 min, and after washing, angiotensin II was added at different concentrations, during 20 min. In another group two stimulations were performed with an interval of 60 min. Angiotensin II antagonists: losartan, PD 123319 and Sar1-Leu8-angiotensin II, alpha 2 adrenergic antagonist: yohimbine, all at 10(-5) M and L-NAME or D-NAME 10(-2) M, were added before stimulation with angiotensin II 10(-6) M or 5.10(-6) M. In another group, besides losartan or PD 123319, yohimbine was added. Nitrite determination was performed with Griess reagent. Angiotensin II 10(-8) to 10(-6) M increased NO metabolite production measured as nitrites referred to the control. In higher concentrations there was a diminution in relation to 10(-6) M. Angiotensin II nitrite release fell in the second stimulation with the hormone in all cases, whereas it was blocked by L-NAME. It was increased by angiotensin II antagonist only at maximal concentrations of the hormone, an effect abolished by yohimbine. Likewise, yohimbine diminished nitrite production at concentrations of angiotensin II of 5.10(-6) but not at 10(-6) M. These results allow us to postulate that NO release induced by angiotensin II would be in part mediated by alpha 2 receptors. Angiotensin II antagonists unmask these effects at maximal concentrations of the hormone, whereas at supramaximal concentrations inhibitory mechanisms would prevail, which would be balanced by alpha 2 activation.
Jerez
S
S
Facultad de Ciencias Naturales e Instituto Miguel Lillo, Universidad Nacional de Tucumán, Instituto Superior de Investigaciones Biológicas (CONICET) y Fundación INELCO, Tucumán, Argentina. sjerez@tucbbs.com.ar
Peral de Bruno
M
M
Coviello
A
A
D058669:Adrenergic alpha-2 Receptor Antagonists; D000804:Angiotensin II / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D001013:Aorta, Thoracic; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D009569:Nitric Oxide / Q000096:biosynthesis / Q000378:metabolism*; D011817:Rabbits; D014662:Vasoconstrictor Agents / Q000037:antagonists & inhibitors / Q000494:pharmacology*
D058669:Adrenergic alpha-2 Receptor Antagonists; D057911:Angiotensin Receptor Antagonists; D014662:Vasoconstrictor Agents; D000804:Angiotensin II; D009569:Nitric Oxide