title: Cicletanine blunts the pulmonary pressor response to acute hypoxia in rats.
abstract: Cicletanine (CIC) recently has been shown to lower systemic arterial pressure in hypertensive animals and man by a mechanism that may involve potentiation of the vasodilator effect of atrial natriuretic peptide (ANP). We previously have shown that ANP prevents acute hypoxia-induced pulmonary vasoconstriction and modulates the severity of chronic hypoxic pulmonary hypertension. The current study tested the hypothesis that CIC inhibits the pulmonary pressor response to acute hypoxia by a cyclic guanosine monophosphate (cGMP)-dependent mechanism. Catheters were placed in the pulmonary arteries of Sprague-Dawley rats through the right jugular vein using a closed chest technique, and in the aorta through the right femoral artery. After a 24 hour recovery, CIC (600 mg/kg) or vehicle was administered orally by gavage to conscious rats 4 hours prior to exposure to 10% oxygen at ambient pressure or to room air. Mean pulmonary arterial pressure (MPAP) and mean systemic arterial pressure (MSAP) and heart rate (HR) were monitored for 3 hours. CIC attenuated the acute pulmonary pressor response to hypoxia (MPAP = 24.5 +/- 1.0 mm Hg in the "hypoxic+CIC" group vs. 29.9 +/- 1.0 mm Hg in the "hypoxic+vehicle" group; p less than 0.05 at 3 hours of hypoxic exposure), but had no significant effect on MSAP or HR. CIC had no effect on MPAP, MSAP, or HR in air control rats. Acute hypoxia caused significant increases in plasma ANP and cGMP and in kidney cGMP content, but CIC administration did not alter these parameters further. This is the first demonstration that acute administration of CIC attenuates the pulmonary pressor response to acute hypoxia in conscious rats.
authors.affiliation: Hypertension Program, University of Alabama, Birmingham 35294.
authors.forename: H
authors.initials: H
authors.lastname: Jin
authors.forename: R H
authors.initials: RH
authors.lastname: Yang
authors.forename: S
authors.initials: S
authors.lastname: Oparil
mesh_terms: D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects*; D004232:Diuretics / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006339:Heart Rate / Q000187:drug effects; D000860:Hypoxia / Q000503:physiopathology*; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology / Q000503:physiopathology; D011651:Pulmonary Artery / Q000187:drug effects / Q000502:physiology* / Q000503:physiopathology; D011725:Pyridines; D051381:Rats; D011919:Rats, Inbred Strains; D012016:Reference Values; D013997:Time Factors
chemical_list: D000959:Antihypertensive Agents; D004232:Diuretics; D011725:Pyridines; C038068:cicletanine