Bradykinin causes selective efferent arteriolar dilation during angiotensin I converting enzyme inhibition.
We studied the effects of interruption of the renin-angiotensin system (RAS) in rats that were volume depleted by water deprivation for 48 hours (AWD) with/without furosemide (AWD + F), a condition known to activate RAS. Following baseline micropuncture, AWD rats (N = 6) were treated with a specific angiotensin II type 1 receptor antagonist (AIIRA; 4 mg/kg body wt bolus i.v. and then continuous infusion) and glomerular hemodynamics compared to those obtained during angiotensin I converting enzyme inhibitor treatment (ACEI; 24 mg/kg bolus i.v. and then continuous infusion). Systemic blood pressure decreased equally following AIIRA and ACEI. Single nephron glomerular filtration rate (SNGFR) increased from baseline following AIIRA (24 nl/min vs. 30, P < 0.025). While a decrease in efferent arteriolar resistance (RE) reduced glomerular capillary pressure (PGC; 67 mm Hg vs. 60, P < 0.05), this change in RE together with decrease in afferent arteriolar resistance (RA), enhanced glomerular plasma flow rate (QA; 80 nl/min vs. 111). Antagonizing angiotensin II receptor increased QA which, together with the tendency to increase glomerular capillary ultrafiltration coefficient, Kf, served to improve glomerular filtration. By contrast, although inhibition of the angiotensin I converting enzyme caused greater vasodilatation, no increase in SNGFR occurred. The lack of response in filtration after ACEI was due to a further fall in PGC to 52 mm Hg (P < 0.01 vs. AIIRA), reflecting profound reduction in RE. Since ACEI but not AIIRA potentiates bradykinin activity we examined effects of a specific bradykinin antagonist (Hoe).(ABSTRACT TRUNCATED AT 250 WORDS)
Kon
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Department of Pediatrics, Vanderbilt University School of Medicine, Nashville, Tennessee.
Fogo
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Ichikawa
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D057911:Angiotensin Receptor Antagonists; D000818:Animals; D001160:Arterioles / Q000187:drug effects* / Q000502:physiology; D001920:Bradykinin / Q000031:analogs & derivatives / Q000494:pharmacology*; D065168:Bradykinin Receptor Antagonists; D004656:Enalapril / Q000494:pharmacology; D005665:Furosemide / Q000494:pharmacology; D007093:Imidazoles / Q000494:pharmacology; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D012084:Renin-Angiotensin System / Q000187:drug effects / Q000502:physiology; D013777:Tetrazoles / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects* / Q000502:physiology; D014868:Water Deprivation / Q000502:physiology
D057911:Angiotensin Receptor Antagonists; D065168:Bradykinin Receptor Antagonists; D007093:Imidazoles; D013777:Tetrazoles; C070967:L 158809; D004656:Enalapril; D005665:Furosemide; C065679:icatibant; D001920:Bradykinin