Angiotensin II-induced venoconstriction involves both AT1 and AT2 receptors and is counterbalanced by nitric oxide.
The venoconstrictor effect of Angiotensin II (Ang II) was investigated in the rat mesenteric venules and portal vein. Mesenteric venules were perfused at a constant rate and reactivity to Ang II (0.1 nmol) was evaluated as changes in the perfusion pressure. Rings of portal vein were mounted in organ baths and curves to Ang II (0.1-100 nmol/L) were generated. In venules, Ang II-contraction (10.6+/-1.1 mmHg) was abolished by losartan (0.9+/-0.3 mmHg*), reduced by PD 123,319 (5.8+/-0.9 mmHg*), increased by L-NAME (16.5+/-1.8 mmHg*) and not altered by indomethacin. In portal veins, curves to Ang II (-logEC50: 8.9+/-0.1 mol/L) were shifted to the right by losartan (-log EC50: 7.5+/-0.1 mol/L*) and by PD 123,319 (-logEC50: 8.0+/-0.1 mol/L*). L-NAME increased the maximal response to Ang II (Emax: 0.91+/-0.1g versus 1.62+/-0.3g*) and indomethacin had no effect. In conclusion, Ang II induces venoconstriction by activating AT1 and AT2 receptors. Data obtained with L-NAME provide evidence that the basal nitric oxide release from the endothelium of the venous system can modulate the Ang II-induced venoconstriction.
Fernandes
Liliam
L
Department of Pharmacology, Institute of Biomedical Sciences I-s/213, University of São Paulo, Av. Prof. Lineu Prestes 1524, 05508 900 São Paulo, SP, Brazil.
Loiola
Rodrigo Azevedo
RA
Tostes
Rita C A
RC
Nigro
Dorothy
D
Fortes
Zuleica Bruno
ZB
de Carvalho
Maria Helena Catelli
MH
D000804:Angiotensin II / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D004791:Enzyme Inhibitors / Q000494:pharmacology; D008297:Male; D008642:Mesenteric Veins / Q000502:physiology*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism*; D009924:Organ Culture Techniques; D011169:Portal Vein / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D044140:Receptor, Angiotensin, Type 1 / Q000378:metabolism*; D044139:Receptor, Angiotensin, Type 2 / Q000378:metabolism*; D014661:Vasoconstriction / Q000187:drug effects* / Q000502:physiology; D014662:Vasoconstrictor Agents / Q000378:metabolism / Q000494:pharmacology*
D004791:Enzyme Inhibitors; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D014662:Vasoconstrictor Agents; D000804:Angiotensin II; D009569:Nitric Oxide; D019331:NG-Nitroarginine Methyl Ester