Angiotensin II-mediated vasodilation is reduced in adult spontaneously hypertensive rats despite enhanced expression of AT2 receptors.
1. The vasodilator action of angiotensin (Ang) II has not yet been demonstrated in spontaneously hypertensive rats (SHR), nor have any possible changes in this response during the development of hypertension. 2. In the present study, the vasodilator effect of AngII was evaluated in the rat isolated, preconstricted mesenteric arterial bed (MAB) from 6- (young) and 24-week-old (adult) SHR and compared with effects on MAB from age-matched normotensive rats (control). 3. Angiotensin II (10-300 nmol) induced vasodilation in noradrenaline (NA)-preconstricted MAB that was greater in vessels from young compared with adult rats in both the control and SHR groups. Angiotensin II-induced vasodilation was reduced by the angiotensin AT(2) receptor antagonist PD 123319 (10 micromol/L), the angiotensin-(1-7) receptor antagonist A779 (1 micromol/L) and the bradykinin B(2) receptor antagonist HOE-140 (0.01 micromol/L), but not by the AT(1) receptor antagonist losartan (30 micromol/L). Expression of AT(2) receptors was weak in vessels from adult control rats compared with that in young control rats, whereas in young SHR AT(2) receptor expression was increased compared with that in young control rats. This increased expression of AT(2) receptors was maintained in adult SHR and there was no significant difference in AT(2) receptor expression between young and old SHR. 4. The findings of the present suggest that AngII induces an AT(2) receptor-mediated vasodilator effect in the MAB via activation of angiotensin-(1-7) and bradykinin receptors, an action that is reduced in adult control rats and adult SHR. In adult control rats, the attenuated response of AngII is probably due to endothelial dysfunction and reduced expression of AT(2) receptors, whereas in adult SHR it is associated with endothelial dysfunction alone. Increased expression of AT(2) receptors in SHR may represent a counteracting response for modulating blood pressure.
Ognibene
D T
DT
Department of Pharmacology, State University of Rio de Janeiro, Rio de Janeiro, Brazil.
Oliveira
P R B
PR
Marins de Carvalho
L C R
LC
Costa
C A
CA
Espinoza
L A
LA
Criddle
D N
DN
Tano
T
T
Soares de Moura
R
R
Resende
A C
AC
D000109:Acetylcholine / Q000494:pharmacology; D000375:Aging; D000804:Angiotensin II / Q000031:analogs & derivatives / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D015153:Blotting, Western; D001920:Bradykinin / Q000031:analogs & derivatives / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000502:physiology*; D007093:Imidazoles / Q000494:pharmacology; D019808:Losartan / Q000494:pharmacology; D008638:Mesenteric Arteries / Q000187:drug effects / Q000378:metabolism; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000378:metabolism; D010446:Peptide Fragments / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D044139:Receptor, Angiotensin, Type 2 / Q000235:genetics / Q000378:metabolism*; D014664:Vasodilation / Q000502:physiology*
C092006:7-Ala-angiotensin (1-7); D007093:Imidazoles; D010446:Peptide Fragments; D011725:Pyridines; D044139:Receptor, Angiotensin, Type 2; D000804:Angiotensin II; C073402:PD 123319; C065679:icatibant; D019001:Nitric Oxide Synthase; D019808:Losartan; D000109:Acetylcholine; D001920:Bradykinin; D019331:NG-Nitroarginine Methyl Ester