Effects of long-term caffeine consumption on renal function in spontaneously hypertensive heart failure prone rats

Our previous studies supported the hypothesis that prolonged administration of caffeine to animals with high-renin hypertension causes progressive det erioration of renal function. However, thus far this hypothesis has been te sted with only a few animal models of hypertension. The aim of this study w as to test this hypothesis further by investigating the effects of long-ter m caffeine consumption on renal function in adult spontaneously hypertensiv e heart failure (SHHF/Mcc-fa(cp)) rats, another model of high-renin hyperte nsion. Lean, male, 9-month-old SHHF/Mcc-fa(cp) rats were randomized to rece ive either normal drinking water (control group) or drinking water containi ng 0.1% caffeine (caffeine group) for 20 weeks. No changes in body weight, food and fluid intake, urine volume, and sodium and potassium excretion wer e found in conscious SHHF/Mcc-fa(cp) rats after 10 or 20 weeks of caffeine treatment. However, caffeine treatment accelerated the time-related decline in renal function and augmented urinary protein excretion. Ten weeks into the protocol, creatinine clearance was 3.6 +/- 0.4 and 5.7 +/- 0.9 L/kg/day in the caffeine group and central group, respectively (p < 0.02), whereas 20 weeks into the study, creatinine clearance was similarly diminished in b oth groups. Proteinuria was greater in the caffeine group compared with the control group at both 10 (928 +/- 131 vs. 439 +/- 21 mg/kg/day, respective ly; p < 0.02) and 20 weeks (1,202 +/- 196 vs. 603 +/- 30 mg/kg/day, respect ively; p < 0.01) into the protocol. After 20 weeks, all animals were anesth etized and instrumented. Caffeine treatment for 20 weeks had no effects on blood pressure, heart rate, or vascular resistance in four examined vascula r beds (abdominal aorta and renal, carotid, and mesenteric arteries). No ch anges in renal hemodynamics and electrolyte excretion were found, whereas s ignificantly lower glomerular filtration rate (GFR; inulin clearance) and c reatinine clearance (p < 0.05) were observed in caffeine-treated animals. T hese data support our hypothesis that prolonged consumption of caffeine has adverse effects on renal function, in high-renin hypertension.