title: Contribution of nitric oxide to the acute antihypertensive effect of blockers of AT1 angiotensin receptors in spontaneously hypertensive rats.
abstract: The acute vasodepressor effect of AT1 angiotensin receptor blockers losartan and CL329167 was compared in spontaneously hypertensive rats (SHR) pretreated and not pretreated with NG-monomethyl-L-arginine (LNMMA; 15 mg/kg i.v. bolus plus infusion at 10 mg/kg/h), an inhibitor of nitric oxide (NO) synthesis. The antihypertensive effect of losartan (30 mg/kg, i.v.) in SHR pretreated with LNMMA (-13 +/- 4 mmHg) was greatly diminished (P < 0.01) relative to the antihypertensive effect of losartan in SHR not pretreated with LNMMA (-44 +/- 8 mmHg). Similarly, the antihypertensive effect of CL329167 (5 mg/kg, i.v.) in SHR pretreated with LNMMA (-12 +/- 3 mmHg) was surpassed (P < 0.01) by the antihypertensive effect in SHR not pretreated with LNMMA. (-41 +/- 4 mmHg). However, pretreatment of SHR with LNMMA did not minimize the vasodepressor effect of prazosin, isoproterenol or sodium nitroprusside. The impairment in vasodepressor responsiveness to losartan in rats pretreated with LNMMA was not demonstrable in rats concurrently receiving sodium nitroprusside to correct for the loss of endogenous NO, or atrial natriuretic peptide which also increases vascular cGMP. These data suggest that a mechanism mediated by NO and/or cGMP is necessary for the full expression of the acute antihypertensive effect of AT1 angiotensin receptor blockers in SHR.
authors.affiliation: Department of Pharmacology, New York Medical College, Valhalla 10595, USA.
authors.forename: V
authors.initials: V
authors.lastname: Cachofeiro
authors.forename: H
authors.initials: H
authors.lastname: Guan
authors.forename: A
authors.initials: A
authors.lastname: Nasjletti
mesh_terms: D057911:Angiotensin Receptor Antagonists; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D019808:Losartan / Q000494:pharmacology*; D008297:Male; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D011799:Quinazolines / Q000494:pharmacology*; D052999:Quinazolinones; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D013777:Tetrazoles / Q000494:pharmacology*; D019323:omega-N-Methylarginine / Q000494:pharmacology
chemical_list: D057911:Angiotensin Receptor Antagonists; D000959:Antihypertensive Agents; C109676:CL 329167; D004791:Enzyme Inhibitors; D011799:Quinazolines; D052999:Quinazolinones; D013777:Tetrazoles; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D019808:Losartan