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(Hypertension. 2001;37:1399.)
© 2001 American Heart Association, Inc.

Scientific Contributions

Coronary Hemodynamic and Ventricular Responses to Angiotensin Type 1 Receptor Inhibition in SHR

Interaction With Angiotensin Type 2 Receptors

Jasmina Varagic; Dinko Susic; Edward D. Frohlich

From the Hypertension Research Laboratory, Alton Ochsner Medical Foundation, New Orleans, La.

Correspondence to Edward D. Frohlich, MD, Alton Ochsner Distinguished Scientist, Alton Ochsner Medical Foundation, 1516 Jefferson Highway, New Orleans, LA 70121.

Abstract—This study was designed to determine the effects of angiotensin II type 1 (AT₁) receptor inhibition on coronary hemodynamics and ventricular mass and hydroxyproline content and the additive effects of angiotensin II type 2 (AT₂) receptor inhibition in spontaneously hypertensive rats (SHR). The selective AT₁ receptor antagonist candesartan (10 mg/kg per day) was administered alone or in combination with the AT₂ receptor antagonist PD 123319 (50 mg/kg per day) for 12 weeks. Control SHR received placebo for the same period. Left and right ventricular coronary blood flow, blood flow reserve, and minimal coronary vascular resistance were determined by using radiomicrospheres in male 35-week-old rats. Mean arterial pressure; total peripheral resistance; left and right ventricular, renal, and aortic weights; and hydroxyproline concentration were also determined. Candesartan reduced mean arterial pressure and left ventricular, renal, and aortic masses, as well as hydroxyproline concentration and minimal coronary vascular resistance of both ventricles. PD 123319 partially prevented the hypotensive effect of AT₁ receptor inhibition and reversed the effect on myocardial hydroxyproline concentration. These data suggest that AT₂ receptors contribute to the hypotensive and antifibrotic effects but not the coronary hemodynamic improvement or reduced left ventricular mass of AT₁ receptor inhibition in these adult SHR.

Key Words: angiotensin II receptors • blood pressure • hemodynamics • rats, inbred SHR • fibrosis

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