Differential effects of eprosartan and losartan at prejunctional angiotensin II receptors.
A comparison was made of the influence of losartan and eprosartan on angiotensin II effects at pre- and postjunctional receptors of the canine pulmonary artery and at prejunctional receptors of the rat left ventricle. To study postjunctional contractile responses to angiotensin II, non-cumulative concentration-response curves were determined; to study prejunctional effects of angiotensin II, the tissues were preincubated with [3H]noradrenaline and then superfused and electrically stimulated (1 Hz, 2 ms, 50 mA, 5 min). Postjunctionally, both losartan and eprosartan caused a parallel shift of the concentration-response curve of angiotensin II to the right (pKd of 8.15 and 8.28, respectively). At the prejunctional level, while eprosartan, in concentrations similar to those which were effective postjunctionally (30-100 nM), antagonized the facilitatory effect on noradrenaline release in both the dog pulmonary artery and the rat ventricle, losartan was ineffective in concentrations up to 1 microM. It is concluded that pre-junctional receptors for angiotensin II in the canine pulmonary artery and in the rat left ventricle are different from postjunctional receptors of the canine pulmonary artery. It is proposed that the prejunctional receptors of these tissues are atypical AT1 or "AT1B-like" receptors.
Guimarães
S
S
Institute of Pharmacology and Therapeutics, Faculty of Medicine, Alameda Hernani Monteiro, Porto, Portugal. sguimara@med.up.pt
Pinheiro
H
H
Tavares
P
P
Loio
A
A
Moura
D
D
D000179:Acrylates / Q000494:pharmacology*; D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D005260:Female; D006352:Heart Ventricles / Q000187:drug effects; D007093:Imidazoles / Q000494:pharmacology*; D019808:Losartan / Q000494:pharmacology*; D008297:Male; D017729:Presynaptic Terminals / Q000187:drug effects* / Q000502:physiology; D011651:Pulmonary Artery / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D011945:Receptors, Angiotensin / Q000502:physiology*; D013876:Thiophenes; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D016276:Ventricular Function
D000179:Acrylates; D000959:Antihypertensive Agents; D007093:Imidazoles; D011945:Receptors, Angiotensin; D013876:Thiophenes; D014662:Vasoconstrictor Agents; D000804:Angiotensin II; C068373:eprosartan; D019808:Losartan