The effects of combined angiotensin converting enzyme inhibition and beta-adrenoceptor blockade on plasma renin activity in anaesthetized dogs.
1. The effects of beta-adrenoceptor blockade on the changes in plasma renin activity (PRA) following angiotensin enzyme (ACE) inhibition were investigated in pentobarbitone-chloralose anaesthetized dogs. 2. ACE-inhibition, with enalapril (2 mg kg-1), caused a significant reduction in systemic arterial blood pressure (BP) with little or no effect on cardiac function, and a significant elevation of plasma renin activity (PRA). By contrast beta-adrenoceptor blockade with atenolol (1 mg kg-1), caused a similar reduction in BP but in addition, significantly reduced cardiac function and PRA. 3. A combination of enalapril with atenolol, caused a significant reduction in BP, cardiac function and PRA, hence there was no elevation of PRA, as was seen following ACE-inhibition with enalapril alone. 4. The observations with beta-adrenoceptor blockade alone, show that there is an important homeostatic role for the renal sympathetic innervation, mediated by beta-adrenoceptors, in controlling basal renin levels. Furthermore, the renal sympathetic innervation appears to be an important contributor to the renin release caused by an ACE-inhibitor as the additional presence of a beta-adrenoceptor blocking agent will prevent this release. 5. BW B385C (2 mg kg-1), which combines both ACE-inhibition and beta-adrenoceptor blocking properties, also produced reductions in BP and cardiac function similar to those seen with the enalapril/atenolol combination. In addition, for an equivalent degree of ACE-inhibition by BW 385C, to that seen with enalapril alone, the elevation of PRA was attenuated. 6. A combination of ACE-inhibition and beta-adrenoceptor blocking activity in a single entity, such as BW B385C, therefore also produces a reduced renin release when compared with an ACE-inhibitor, such as enalapril. This provides further confirmation of the importance of the renal sympathetic innervation in the renin response to ACE-inhibition, and supports the concept of combining ACEinhibition with beta-adrenoceptor blockade.
Cambridge
D
D
Department of Pharmacology, Wellcome Research Laboratories, Beckenham, Kent.
Whiting
M V
MV
Butterfield
L J
LJ
Allan
G
G
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000758:Anesthesia; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D001262:Atenolol / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D004285:Dogs; D004656:Enalapril / Q000494:pharmacology; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D007211:Indoles / Q000494:pharmacology; D008297:Male; D011412:Propanolamines / Q000494:pharmacology; D012083:Renin / Q000097:blood*
D000319:Adrenergic beta-Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D007211:Indoles; D011412:Propanolamines; C055304:BW-A 575C; D001262:Atenolol; D004656:Enalapril; D012083:Renin