Renal extraction of angiotensin II.
Angiotensin II regulates many aspects of renal function and thereby influences long-term blood pressure. The effects of angiotensin II on the kidney have been exhaustively studied; however, the converse (i.e., effects of the kidney on angiotensin II) has received little attention. Accordingly, the focus of this study was to determine whether renal degradation of angiotensin II is regulated by chronic levels of angiotensin II or long-term levels of blood pressure. Twenty hypertensive rats and 22 normotensive rats were treated for 1 week with either vehicle, angiotensin II (50 ng/kg/min, subcutaneously) or captopril (100 mg/kg/day, orally). Right kidney vascular resistance was measured during infusions of angiotensin II into the left renal artery or vena cava at the level of left renal vein. Dose-response data were curve-fitted, and the extraction of angiotensin II by the left kidney was calculated by comparing the doses of angiotensin II required to elicit equal increases in right renal vascular resistance during intravenous versus left intrarenal artery infusions. Renal extraction of angiotensin II was high (mean, 81%) and demonstrated little animal-to-animal variation (coefficient of variation, 23%; standard deviation, 19%). Renal extraction of angiotensin II was independent of hypertension (P = 0.257) or previous chronic exposure to angiotensin II or captopril (P = 0.270), and there was no interaction between hypertension and chronic exposure to angiotensin II or captopril (P = 0.950). We conclude that renal degradation of angiotensin II is constitutively high, is unaffected by chronic levels of arterial blood pressure, and is independent of long-term changes in levels of angiotensin II.
Jackson
Edwin K
EK
Center for Clinical Pharmacology, University of Pittsburgh School of Medicine, 623 Scaife Hall, 3550 Terrace Street, Pittsburgh, PA 15261, USA. edj@pitt.edu
Herzer
William A
WA
D000804:Angiotensin II / Q000378:metabolism* / Q000494:pharmacology; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D002216:Captopril / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D007262:Infusions, Intravenous; D007668:Kidney / Q000378:metabolism*; D008297:Male; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D012079:Renal Circulation / Q000187:drug effects / Q000502:physiology
D000806:Angiotensin-Converting Enzyme Inhibitors; D000804:Angiotensin II; D002216:Captopril