Constrictor and dilator effects of angiotensin II on cerebral arterioles.
OBJECTIVE
In light of the equivocal data on the cerebral vasoconstrictor and vasodilator actions of angiotensin II (Ang II) and the potential clinical importance of this, we investigated the effects of Ang II on rat pial arterioles.


METHODS
We determined the effect of Ang I (3.10(-6) mol/L) in the absence and presence of the converting enzyme inhibitor, captopril (10(-5) mol/L) in cerebral arterioles of male Wistar rats (open-skull preparation), and those of Ang II (3.10(-12) to 3.10(-6) mol/L) in the absence and presence of the Ang II receptor (AT1) antagonist, telmisartan (10(-5) mol/L) or the AT2 antagonist, PD123319 (10(-5) mol/L). We examined the effect of PD123319 (10(-5) mol/L) and the Ca2+-activated K+ (BKCa) channel blocker, tetraethylammonium (10(-4) mol/L) on the Ang II responses in the presence of telmisartan (10(-5) mol/L).


RESULTS
Ang II-induced dose-dependent constriction with a maximum decrease of -20.1+/-1.0% at 10(-6) mol/L. Captopril significantly decreased Ang I-induced vasoconstriction (-4.0+/-0.9 versus -21.3+/-2.5%; n=4). Telmisartan reversed Ang II-induced vasoconstriction (9.5+/-2.5 versus -20.1+/-1% at 10(-6) mol/L; n=5). PD123319 significantly increased Ang II-induced vasoconstriction (-12.9+/-0.8 versus -10.2+/-0.4% at 10(-6) mol/L; n=5). PD123319 abolished (-2.6+/-0.7 versus 9.3+/-1.1% at 10(-6) mol/L; n=5) whereas tetraethylammonium reversed (-12.1+/-1.6 versus 9.9+/-1.0% at 10(-6) mol/L; n=4) Ang II-induced vasodilatation in the presence of telmisartan.


CONCLUSIONS
Angiotensin is converted locally into Ang II; the overall effect of Ang II is vasoconstrictor following stimulation of the AT1 receptor, but a vasodilator response can be evoked following stimulation of the AT2 receptor and activation of BKCa.
Vincent
Jean-Martin
JM
Laboratoire de Pharmacologie, Faculté de Pharmacie, l'Université Henri Poincaré-Nancy I, 5 rue Albert Lebrun, 54000 Nancy, France.
Kwan
Yiu Wa
YW
Chan
Siu Lung
SL
Perrin-Sarrado
Caroline
C
Atkinson
Jeffrey
J
Chillon
Jean-Marc
JM
D000804:Angiotensin II / Q000494:pharmacology* / Q000502:physiology*; D000818:Animals; D001160:Arterioles / Q000187:drug effects / Q000502:physiology*; D001562:Benzimidazoles / Q000494:pharmacology; D001565:Benzoates / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002216:Captopril / Q000494:pharmacology; D002536:Cerebral Arteries / Q000187:drug effects / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D007093:Imidazoles / Q000494:pharmacology; D008297:Male; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D044140:Receptor, Angiotensin, Type 1 / Q000187:drug effects / Q000502:physiology; D011945:Receptors, Angiotensin / Q000187:drug effects / Q000502:physiology; D000077333:Telmisartan; D019789:Tetraethylammonium / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology*; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*
D001562:Benzimidazoles; D001565:Benzoates; D002121:Calcium Channel Blockers; D007093:Imidazoles; D011725:Pyridines; D044140:Receptor, Angiotensin, Type 1; D011945:Receptors, Angiotensin; D000804:Angiotensin II; C073402:PD 123319; D019789:Tetraethylammonium; D002216:Captopril; D000077333:Telmisartan