Resistance to blockade by saralasin of effect of ACE inhibitors in conscious sodium-restricted dog.
Comparison of the effect of captopril and enalaprilat was made on mean systemic arterial blood pressure (BP), renal blood flow (RBF), and renal vascular resistance (RVR) of conscious sodium-replete and sodium-restricted dogs (plasma renin activity = 6.66 ng angiotensin I.ml-1.h-1). BP was decreased by -8 +/- 2 mmHg and RBF was increased by 34 +/- 12 ml/min with captopril given intravenously and by -5 +/- 2 mmHg and 28 +/- 7 ml/min with enalaprilat in sodium-replete dogs. The respective changes in BP and RBF in sodium-restricted dogs were -29 +/- 2 mmHg and 62 +/- 12 ml/min with captopril and -25 +/- 6 mmHg and 53 +/- 18 ml/min with enalaprilat. Saralasin infused intra-arterially to the kidney significantly blocked the increase in RBF seen after angiotensin-converting enzyme (ACE) inhibition in sodium-replete dogs, and reduced the increase in RBF in sodium-restricted dogs, but the latter effect was not statistically significant. A more moderate increase in plasma renin activity was established in another group of sodium-restricted dogs, and saralasin was administered intravenously instead of intra-arterially. Enalaprilat increased RBF in these dogs in the presence of a saralasin blockade (42 +/- 7 ml/min), and this effect was not significantly changed by prior administration of indomethacin (28 +/- 6 ml/min). The results suggest that blockade of the influence of the renin-angiotensin system and possibly another vasodilator mechanism, such as kinin potentiation, account for the increase in RBF after ACE inhibition in the low-sodium state.
Zimmerman
B G
BG
Department of Pharmacology, University of Minnesota, Minneapolis 55455.
Goering
J L
JL
Raich
P C
PC
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D001783:Blood Flow Velocity / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D001920:Bradykinin / Q000494:pharmacology; D002216:Captopril / Q000494:pharmacology; D004039:Diet, Sodium-Restricted; D004285:Dogs; D004656:Enalapril / Q000031:analogs & derivatives / Q000494:pharmacology; D015773:Enalaprilat; D005260:Female; D007668:Kidney / Q000098:blood supply* / Q000187:drug effects; D008297:Male; D012079:Renal Circulation / Q000187:drug effects; D012083:Renin / Q000097:blood; D012084:Renin-Angiotensin System / Q000187:drug effects; D012504:Saralasin / Q000494:pharmacology*; D014655:Vascular Resistance / Q000187:drug effects
D000806:Angiotensin-Converting Enzyme Inhibitors; D004656:Enalapril; D002216:Captopril; D012083:Renin; D015773:Enalaprilat; D012504:Saralasin; D001920:Bradykinin