AT(2) receptor-mediated vasodilation in the heart: effect of myocardial infarction.
To investigate the functional consequences of postinfarct cardiac angiotensin (ANG) type 2 (AT(2)) receptor upregulation, rats underwent coronary artery ligation or sham operation and were infused with ANG II 3-4 wk later, when scar formation is complete. ANG II increased mean arterial pressure (MAP) more modestly in infarcted animals than in sham animals. The AT(1) receptor antagonist irbesartan, but not the AT(2) receptor antagonist PD123319, decreased MAP and antagonized the ANG II-mediated systemic hemodynamic effects. Myocardial (MVC) but not renal vascular conductance (RVC) was diminished in infarcted versus sham rats. ANG II did not affect MVC and reduced RVC in all rats. MVC was unaffected by irbesartan and PD123319 in all animals. However, with PD123319, ANG II reduced MVC in sham but not infarcted animals, and, with irbesartan, ANG II increased MVC in infarcted but not sham animals. Irbesartan increased RVC and antagonized the ANG II-mediated renal effects in all animals. RVC, at baseline or with ANG II, was not affected by PD123319 in infarcted and sham animals. In conclusion, coronary but not renal AT(2) receptor stimulation results in vasodilation, and this effect is enhanced in infarcted rats.
Schuijt
M P
MP
Department of Pharmacology, Erasmus University Rotterdam, The Netherlands.
Basdew
M
M
van Veghel
R
R
de Vries
R
R
Saxena
P R
PR
Schoemaker
R G
RG
Danser
A H
AH
D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D001713:Biphenyl Compounds / Q000494:pharmacology; D002302:Cardiac Output / Q000187:drug effects / Q000502:physiology; D003326:Coronary Circulation / Q000187:drug effects / Q000502:physiology*; D006333:Heart Failure / Q000378:metabolism; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D007093:Imidazoles / Q000494:pharmacology; D000077405:Irbesartan; D008297:Male; D009203:Myocardial Infarction / Q000378:metabolism* / Q000401:mortality; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin / Q000378:metabolism*; D012079:Renal Circulation / Q000187:drug effects / Q000502:physiology; D015996:Survival Rate; D013777:Tetrazoles / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*
D000959:Antihypertensive Agents; D001713:Biphenyl Compounds; D007093:Imidazoles; D011725:Pyridines; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin; D013777:Tetrazoles; D014662:Vasoconstrictor Agents; D000804:Angiotensin II; C073402:PD 123319; D000077405:Irbesartan