Plasma kinin levels in acute renovascular hypertension in dogs.
The role of kinins in the hypertensive response to acute renal artery constriction (RAC) was examined in the dog. RAC resulted in an increase in systemic arterial pressure (SAP) from 144 +/- 6 to 155 +/- 4 mm HG (p less than 0.05). Simultaneously, arterial plasma bradykinin decreased from 2.3 +/- 0.2 to 1.4 +/- 0.1 ng/ml (p greater than 0.01), while renal venous bradykinin remained unchanged (2.3 +/- 0.2 to 2.0 +/- 0.4 ng/ml, p greater than 0.05). At the same time urinary kallikrein decreased from 55 +/- 6 to 33 +/- 4 milliesterase units (mEU)/min (p less than 0.05), while urinary kinin decreased from 3.2 +/- 0.4 to 1.9 +/- 0.3 ng/min (p less than 0.05). There was a significant correlation between the decrease in arterial bradykinin and the rise in SAP induced by RAC (p less than 0.01). Administration of the dipeptidyl hydrolase inhibitor SQ20881 during RAC reduced angiotensin-converting enzyme levels from 578 +/- 86 to 10 +/- 0.0 mU/ml (p less than 0.005). There was an associated increase in arterial bradykinin (1.4 +/- 0.1 to 5.8 +/- 0.8 ng/ml, p less than 0.001), renal venous bradykinin (2.0 +/- 0.4 to 5.7 +/- 0.5 ng/ml, p less than 0.005), and urinary kinin (1.9 +/- 0.3 to 5.0 +/- 0.7 ng/min, p less than 0.01) in conjunction with return of SAP to control levels. Urinary kallikrein, however, remained depressed following SQ20881 (33 +/- 4 to 30 +/- 5 mEU/min, p greater than 0.05). These results suggest that (1) decreases in circulating BK may potentiate the vasoconstrictor effect of angiotensin II and contribute to the hypertension induced by RAC, and (2) urinary kallikrein is an unreliable marker of changes in plasma bradykinin in this model of hypertension.
D000804:Angiotensin II / Q000502:physiology; D000818:Animals; D001920:Bradykinin / Q000097:blood; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases / Q000037:antagonists & inhibitors; D004285:Dogs; D005260:Female; D005919:Glomerular Filtration Rate; D006978:Hypertension, Renovascular / Q000097:blood* / Q000201:enzymology / Q000652:urine; D007610:Kallikreins / Q000652:urine; D007705:Kinins / Q000097:blood* / Q000502:physiology / Q000652:urine; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism; D011458:Prostaglandins E / Q000097:blood; D012079:Renal Circulation; D012083:Renin / Q000097:blood / Q000378:metabolism; D013722:Teprotide / Q000494:pharmacology; D014655:Vascular Resistance
D007705:Kinins; D011458:Prostaglandins E; D000804:Angiotensin II; D013722:Teprotide; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases; D007703:Peptidyl-Dipeptidase A; D007610:Kallikreins; D012083:Renin; D001920:Bradykinin