4.5 Article

Cardiorenal effects of adenosine subtype 1 (A1) receptor inhibition in an experimental model of heart failure

Journal

JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS
Volume 194, Issue 5, Pages 603-609

Publisher

ELSEVIER SCIENCE INC
DOI: 10.1016/S1072-7515(02)01136-5

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Funding

  1. NHLBI NIH HHS [HL81691] Funding Source: Medline

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BACKGROUND: Elaboration of a number of bioactive substances, including adenosine, occurs in heart failure (HF). Adenosine, through the adenosine subtype I (A(1)) receptor, can reduce renal perfusion pressure and glomerular filtration rate and increase tubular sodium reabsorption, which can affect natriuresis and aquaresis. Accordingly, the present study examined the acute effects of selective A(1) receptor blockade on hemodynamics and renal function in a model of HF. STUDY DESIGN: HF was induced in adult pigs (n = 19) by chronic pacing (240 beats/min for 3 weeks). The pigs were then instrumented for hemodynamics and renal function measurements. After baseline measurements were taken, pigs received either A, block {1 mg/kg BG9719 (1,3-dipropyl-8-[2(5,6-epoxynorbornyl)] xanthine; n = 9)1 or infusion of vehicle (n = 10), and measurements were repeated at intervals for up to 2 hours. Normal controls (n = 7) were included for comparison. RESULTS: Cardiac output remained unchanged between the A, block and vehicle groups throughout the study. Pulmonary vascular resistance fell 38% from baseline at 10 minutes post-A(1) block in the HF group (p < 0.05) with no change in the vehicle group. At 10 minutes post-A(1) block, urine flow increased sixfold and sodium excretion increased over 10-fold (for both, p < 0.05) with no change in the vehicle group. At 10 minutes post-A(1) block, creatinine clearance increased with no change in the vehicle group. At 10 minutes post-A(1) block, plasma renin activity had increased over threefold (p < 0.05), and it returned to baseline levels by 30 minutes post-A(1) block, CONCLUSIONS: The unique findings from this study were threefold. First, increased A(1) receptor activation contributes to renal mediated fluid retention in HE Second, selective A(1) blockade can induce diuresis without hemodynamic compromise and with possible benefit to pulmonary resistance in a model of HE A(1) blockade transiently increased plasma renin activity with no change in hemodynamics. These unique results suggest that selective A(1) blockade can be a useful adjunctive diuretic in the setting of HF.

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