The present study was aimed to determine the effect of caffeine on the development of renal hypertension. Two-kidney, 1-clip (2K1C) hypertension and deoxycorticosterone acetate (DOCA, 200 mg/kg, subcutaneous implantation) – salt (0.9% NaCl drinking) hypertension were instituted in Sprague-Dawley rats. They were then grouped into two groups each: one was supplemented with caffeine (0.1%) in their drinking solution and the other was not. Systolic blood pressure was measured up to 24 days. Caffeine exacerbated the development of 2K1C hypertension in association with a higher plasma renin concentration (PRC). Caffeine ingestion, however, did not exacerbate but ameliorated DOCA-salt hypertension in which PRC was comparable between the caffeine-ingested and control groups. Concentrations of plasma atrial natriuretic peptide (pANP) were significantly different between the caffeine-ingested and control groups neither in 2K1C nor in DOCA-salt rats, suggesting that ANP was not responsible for the modified blood pressure. Acute caffeine infusion (350 μg/min, 30 min) in anesthetized normotensive rats caused increases in urinary excretion (volume and sodium) and in PRC without significantly affecting the blood pressure and pANP. These results suggest that caffeine specifically exacerbates 2K1C hypertension through increasing renin release whereas it ameliorates DOCA-salt hypertension possibly through increasing renal excretion.

Background:Although endogenous creatinine clearance is often used as an indicator for the glomerular filtration rate (GFR), it may result in an overestimation due to its tubular secretion. Since cimetidine is known to inhibit tubular secretion of creatinine, it may improve the accuracy of the creatinine clearance in measuring GFR.Methods:Creatinine clearance (Ccr) was compared with iothalamate clearance (C10th) during oral administration of either placebo or cimetidine in 25 patients with varying degrees of renal dysfunction.Results:Cimetidine itself had no effect on C10th but decreased Ccr, improving its validity, as measured by a significant decrease of Ccr/C10th from 1.72 during placebo to 1.17 during cimetidine administration. The degree of overestimation measured by the Ccr was more pronounced in those with more severe renal dysfunction. A significant inverse correlation was noted between Ccr/C10th and GFR. No apparent side effect due to cimetidine was noted.Conclusions:These results suggest that cimetidine improves the accuracy of Ccr as an indicator for GFR in patients with varying degrees of renal dysfunction.