Hypovolaemia-induced vasodilatation during angiotensin AT1 receptor blockade: role of the AT2 receptor.
AT(1) receptor antagonists may interfere with the haemodynamic determinants of arterial pressure either directly or indirectly through the stimulation of AT(2) receptor provided Ang II is available to interact with them. In order to evaluate the counteracting haemodynamic effect of AT(2) receptor, a prospective, randomized, controlled experimental study was carried out in anaesthetised juvenile pigs. Pigs were randomly assigned to receive placebo (n = 6), valsartan, an AT(1) receptor antagonist (a-AT(1) group; n = 6), or valsartan and PD 123319, an AT(2) receptor antagonist (a-AT(1-2) group; n = 6) after anaesthesia and before hypovolaemia by 20% of the total estimated blood volume. Thirty minutes after bleeding, the mean arterial pressure decreased significantly and similarly in the three groups (25-30%). The placebo group had a significant decrease in cardiac output (CO) without significant change in systemic vascular resistance (SVR). Conversely, in the a-AT(1) group, SVR decreased significantly with a moderate change in CO and addition of the AT(2) antagonist to the AT(1) antagonist (a-AT(1-2) group) did not abolish the lowering in SVR. The results suggest that AT(2) receptor has only a small if any contribution in the vasodilatation observed in the AT(1)-blockade group.
Ryckwaert
Frédérique
F
Faculté de Médecine, Université-Montpellier I, Service d'anesthésie-réanimation D, Hopital Arnaud de Villeneuve, avenue du Doyen Giraud, 34295 Montpellier, France. f-ryckwaert@chu-montpellier.fr
Colson
Pascal H
PH
D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology*; D057912:Angiotensin II Type 2 Receptor Blockers; D000818:Animals; D005260:Female; D020896:Hypovolemia / Q000503:physiopathology*; D044140:Receptor, Angiotensin, Type 1 / Q000502:physiology*; D044139:Receptor, Angiotensin, Type 2 / Q000502:physiology*; D013552:Swine; D013777:Tetrazoles / Q000494:pharmacology; D014633:Valine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000068756:Valsartan; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*
D047228:Angiotensin II Type 1 Receptor Blockers; D057912:Angiotensin II Type 2 Receptor Blockers; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D013777:Tetrazoles; D000068756:Valsartan; D014633:Valine