title: Resistance to blockade by saralasin of effect of ACE inhibitors in conscious sodium-restricted dog.
abstract: 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.
authors.affiliation: Department of Pharmacology, University of Minnesota, Minneapolis 55455.
authors.forename: B G
authors.initials: BG
authors.lastname: Zimmerman
authors.forename: J L
authors.initials: JL
authors.lastname: Goering
authors.forename: P C
authors.initials: PC
authors.lastname: Raich
mesh_terms: 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
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D004656:Enalapril; D002216:Captopril; D012083:Renin; D015773:Enalaprilat; D012504:Saralasin; D001920:Bradykinin