The effect of kinin and prostaglandin inhibitors on the renal response to angiotensin-converting enzyme inhibition: a micropuncture study in the dog.
It has been suggested that angiotensin-converting enzyme (ACE) inhibition is accompanied by enhanced bradykinin and prostaglandin activities, which may contribute to the renal haemodynamic actions of ACE inhibitors. Therefore we investigated renal function by clearance and micropuncture techniques in dogs maintained either on normal or low-salt diet before and after ACE inhibition with an i.v. bolus of 0.1 mg/kg ramiprilat followed by an infusion of 5 micrograms kg-1 min-1. Subgroups each comprising six dogs were also treated with either HOE-140, a bradykinin B2 receptor antagonist, or the cyclooxygenase inhibitor indomethacin. In general, renal effects of ramiprilat were more pronounced in dogs fed on low salt than in those on normal diet. In dogs on low salt, the mean arterial pressure decreased by 20% 20 min after ramiprilat application, whereas the total renal blood flow rose by 71% from 4.71 to 8.06 ml min-1 g kidney weight-1 and the glomerular filtration rate (GFR) by 28% from 0.74 to 0.95 ml min-1 g-1. Single-nephron glomerular blood flow and single-nephron GFR rose by 55% and 23% respectively. The total and the single-nephron filtration fraction decreased by 25% and 23% respectively. There were no substantial changes in glomerular and peritubular capillary and tubular pressures, but a significant increase in the ultrafiltration coefficient, Kf, by 103% from 3.55 nl/mmHg to 7.19 nl/mmHg (26.7-54.0 nl/kPa) was observed. Afferent and efferent arteriolar resistances decreased in parallel by 55% and 47%.(ABSTRACT TRUNCATED AT 250 WORDS)
Heller
J
J
Department of Experimental Medicine, Institute of Clinical Experimental Medicine, Prague, Czech Republic.
Kramer
H J
HJ
Horácek
V
V
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D001920:Bradykinin / Q000037:antagonists & inhibitors*; D003627:Data Interpretation, Statistical; D004032:Diet; D004039:Diet, Sodium-Restricted; D004285:Dogs; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects; D008297:Male; D011448:Prostaglandin Antagonists / Q000494:pharmacology*; D011677:Punctures; D017257:Ramipril / Q000031:analogs & derivatives / Q000494:pharmacology; D012079:Renal Circulation / Q000187:drug effects*
D000806:Angiotensin-Converting Enzyme Inhibitors; D011448:Prostaglandin Antagonists; C052549:ramiprilat; D017257:Ramipril; D001920:Bradykinin