Indirect evidence against a role of the kinin system in the renal hemodynamic effect of captopril in the rat.
The effects of acute saralasin (SAR) and captopril (SQ) administration on arterial pressure (AP), plasma renin activity (PRA), urinary excretion of water and electrolytes, glomerular filtration rate (GFR), renal blood flow (RBF), and glomerular blood flow (GBF) distribution (microsphere technique) were assessed in rats with activation of the renal renin and kallikrein systems (that is, chronic sodium depletion). In both groups AP decreased, and PRA and RBF increased markedly. Blood flow to outermost (C1) glomeruli was (in nl/min/g of kidney wt) 270 +/- 35 in SAR and 219 +/- 20 in the SQ group (NS when compared to 208 +/- 9 in control chronically sodium-depleted rats). Blood flow to innermost glomeruli (C4) strikingly increased from 95 +/- 10 (control) to 216 +/- 21 (SAR) and 180 +/- 13 (SQ group). Hence, preferential vasodilatation of innermost glomeruli occurred (C1/C4 ratio of 2.18 +/- 0.27 in control, 1.26 +/- 0.11 in SAR, and 1.25 +/- 0.07 in SQ rats). Chronic (6 days) administration of SQ was associated with a rapid and marked increase in water and sodium excretion. At the end of the study, RBF was higher than control, and GBF distribution was similar to that observed in acutely treated rats (C1/C4 ratio of 1.16 +/- 0.10). These results suggest that angiotensin plays a significant role in the systemic and renal hemodynamic changes associated with chronic sodium depletion. The similarity of the changes induced by SAR and SQ provides an indirect evidence against an effective role of the renal kallikrein system in the effect of captopril.
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002216:Captopril / Q000494:pharmacology*; D005919:Glomerular Filtration Rate / Q000187:drug effects; D007668:Kidney / Q000098:blood supply*; D008297:Male; D011392:Proline / Q000031:analogs & derivatives*; D051381:Rats; D012039:Regional Blood Flow / Q000187:drug effects; D012083:Renin / Q000097:blood*; D012504:Saralasin / Q000494:pharmacology; D014882:Water-Electrolyte Balance / Q000187:drug effects
D011392:Proline; D002216:Captopril; D012083:Renin; D012504:Saralasin