Evidence for the involvement of different receptor subtypes in the pre- and postjunctional actions of angiotensin II at rat sympathetic neuroeffector sites.
1. The effects of the nonpeptide angiotensin II receptor (AT) antagonists losartan and PD 123319 on actions of angiotensin II in the rat caudal artery and rat vas deferens preparations were investigated. 2. Angiotensin II (1.0 microM) increased perfusion pressure in isolated segments of the rat caudal artery. This increase in perfusion pressure was prevented by the AT1-antagonist, losartan (0.1 microM) but was not affected by the AT2-antagonist, PD 123319 (0.1 microM). 3. Angiotensin II (0.1-3.0 microM) produced a concentration-dependent enhancement of the stimulation-induced (S-I) efflux of [3H]-noradrenaline from isolated segments of rat caudal artery in which the noradrenergic transmitter stores had been labelled with [3H]-noradrenaline. The maximum enhancement of S-I efflux was approximately 60% with 1.0 microM angiotensin II. 4. Losartan (0.01 and 0.1 microM) reduced the enhancement of S-I efflux produced by 1.0 microM angiotensin II in the caudal artery. 5. PD 123319 (0.01 microM) did not affect the enhancement of S-I efflux produced by angiotensin II (1.0 microM) in the caudal artery. However, in a higher concentration (0.1 microM), PD 123319 reduced the enhancement of S-I efflux produced by 1.0 microM angiotensin II. 6. Angiotensin II produced concentration-dependent enhancement of the purinergic twitch responses (1 pulse/60 s) in the rat vas deferens. 7. Losartan (0.03 microM) and PD 123319 (0.03 microM) each reduced the angiotensin II-induced enhancement of the twitch responses in the rat vas deferens. 8. These findings indicate that the enhancement of sympathetic neuroeffector transmission in both the caudal artery and vas deferens of the rat involves angiotensin receptor subtype(s) sensitive to both losartan and PD 123319. In contrast, the direct vasoconstrictor effect of angiotensin II in the rat caudal artery involves activation of a receptor subtype sensitive only to losartan.
Cox
S L
SL
Department of Medical Laboratory Science, RMIT, Melbourne, Victoria, Australia.
Ben
A
A
Story
D F
DF
Ziogas
J
J
D000804:Angiotensin II / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000494:pharmacology*; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D001713:Biphenyl Compounds / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D004558:Electric Stimulation; D005260:Female; D007093:Imidazoles / Q000494:pharmacology; D066298:In Vitro Techniques; D019808:Losartan; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D009451:Neuroeffector Junction / Q000187:drug effects*; D009638:Norepinephrine / Q000378:metabolism; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013564:Sympathetic Nervous System / Q000187:drug effects*; D013777:Tetrazoles / Q000494:pharmacology; D014649:Vas Deferens / Q000187:drug effects / Q000294:innervation
D057911:Angiotensin Receptor Antagonists; D001713:Biphenyl Compounds; D007093:Imidazoles; D011725:Pyridines; D013777:Tetrazoles; D000804:Angiotensin II; C073402:PD 123319; D019808:Losartan; D009638:Norepinephrine