Caffeine increases renal renin secretion in a rat model of genetic heart failure

In a previous study, we showed that caffeine (CAFF) increases basal renin s ecretion by blocking intrarenal adenosine receptors and, when sympathetic a ctivity is increased, augments renin release in part by blockade of brain a denosine receptors, leading to increased central sympathetic tone. The purp ose of this study was to investigate the effects of GAFF treatment on neuro humoral status and heart performance in experimental heart failure. Two ser ies of experiments were performed. First, the effects of GAFF (10 mg/kg + 1 50 mu g/min over 40 min) on heart performance (time-pressure variables) and neurohumoral status were studied in conscious, 9-month-old Wistar-Kyoto (W KY) rats, spontaneously hypertensive rats (SHRs), and spontaneously hyperte nsive heart failure (SHHF/Mcc-fa(cp)) rats. Second, caffeine (0.1% in drink ing water) was given for 10 days to 14-month-old SHHF/Mcc-fa(cp) rats, and cardiac performance, renal function, and neurohumoral status determined in vivo. GAFF infusion increased heart rate, left ventricular peak systolic pr essure, and workload in hypertensive (SHRs and SHHF), but not in normotensi ve (WKY) animals and had no effects on cardiac contractility in all three s trains. GAFF increased plasma renin activity (PRA), norepinephrine (NE), an d epinephrine (E) levels in all three strains [treatment effect, p < 0.001, 2F analysis of variance (ANOVA)], and these effects were greater in hypert ensive (SHRs and SHHF) animals as compared with normotensive WKY rats (p < 0.015). Ten-day GAFF treatment in 14-month-old SHHF did not change measured cardiac time-pressure variables, or hemodynamic or renal excretory functio n parameters that can affect renin secretion. However, GAFF treatment signi ficantly increased renal renin secretion (71.1 +/- 19.2 vs. 9.5 +/- 5.8 ng Ang I/h/min/kg for caffeine and control group, respectively; p < 0.01). In summary, acute administration of GAFF increases workload, but has no effect s on cardiac contractility in conscious SHHF rats. The cardiac effects are accompanied by increased renin release and NE and E plasma levels. Moreover , this study provides the first evidence that short-term caffeine consumpti on increases renal renin secretion in heart failure, an effect most likely due to the blockade of intrarenal adenosine receptors. It is possible that long-term activation of neurohumoral mechanisms by GAFF could have adverse effects in heart failure.