AT(2) RECEPTOR STIMULATION INCREASES AORTIC CYCLIC-GMP IN SHRSP BY A KININ-DEPENDENT MECHANISM

Citation
P. Gohlke et al., AT(2) RECEPTOR STIMULATION INCREASES AORTIC CYCLIC-GMP IN SHRSP BY A KININ-DEPENDENT MECHANISM, Hypertension, 31(1), 1998, pp. 349-355
Citations number
37
Categorie Soggetti
Peripheal Vascular Diseas
Journal title
ISSN journal
0194911X
Volume
31
Issue
1
Year of publication
1998
Part
2
Supplement
S
Pages
349 - 355
Database
ISI
SICI code
0194-911X(1998)31:1<349:ARSIAC>2.0.ZU;2-W
Abstract
In the present study we tested the hypothesis whether an angiotensin A T(2) receptor-mediated stimulation of the bradykinin (BK)/nitric oxide (NO) system can account for the effects of AT(1) receptor antagonism on aortic cGMP described previously in SHRSP. Adult SHRSP were treated for 4 hours with angiotensin II (ANG II) (30 ng/kg per min IV) or veh icle (0.9% NaCl IV). Animals were pretreated with vehicle, losartan (1 00 mg/kg PO), PD 123319 (30 mg/kg IV), losartan plus PD 123319, icatib ant (500 mu g/kg IV), N-G-nitro-L-arginine methyl ester (L-NAME; 1 mg/ kg IV), or minoxidil (3 mg/kg IV). Mean arterial blood pressure (MAP) was continuously monitored over the 4-hour experimental period, and pl asma ANG II and aortic cGMP were measured by RIA at the end of the stu dy. ANG II infusion over 4 hours raised MAP by about 20 mm Hg. Losarta n alone or losartan plus ANG II as well as minoxidil plus ANG II marke dly reduced blood pressure when compared to vehicle-treated or ANG II- treated animals, respectively. Plasma levels of ANG II were increased 2-fold by ANG II infusion alone or by ANG II in combination with icati bant, L-NAME, or minoxidil. The increase in plasma ANG II levels was e ven more pronounced after losartan treatment. Aortic cGMP content was significantly increased by ANG II, losartan, losartan plus ANG II, and minoxidil plus ANG II by 60%, 45%, 68%, and 52%, respectively (P<.05) . The effects of ANG II and of losartan plus ANG II on aortic cGMP con tent were both blocked by cotreatment with the AT(2) receptor antagoni st PD 123319. Icatibant and L-NAME abolished the effects of ANG II on aortic cGMP. Our results demonstrate the following: (1) ANG II increas es aortic cGMP by an AT(2) receptor-mediated action because the effect could be prevented by an AT(2) receptor antagonist; (2) the effect of ANG II was not secondary to blood pressure increase because it remain ed under reduction of MAP with minoxidil; (3) losartan increased aorti c cGMP most likely by increasing plasma ANG II levels with a subsequen t stimulation of AT(2) receptors; and (4) the effects of AT(2) recepto r stimulation are mediated by BK and, subsequently, NO because they we re abolished by B-2 receptor blockade as well as by NO synthase inhibi tion.