The effects of combined angiotensin converting enzyme inhibition and β‐adrenoceptor blockade on plasma renin activity in anaesthetized dogs

• Published in: British journal of pharmacology 1992-06, Vol.106 (2), p.342-347
• Main Authors: Cambridge, D., Whiting, M.V., Butterfield, L.J., Allan, G.
• Format: Article
• Language: English
• Subjects: ACE‐inhibition/β‐adrenoceptor blockade; Adrenergic beta-Antagonists - pharmacology; Anesthesia; Angiotensin-Converting Enzyme Inhibitors - pharmacology; Animals; Atenolol - pharmacology; Blood Pressure - drug effects; BW B385C; Dogs; Enalapril - pharmacology; Female; Heart Rate - drug effects; Indoles - pharmacology; Male; plasma renin activity; Propanolamines - pharmacology; Renin - blood
• ISSN: 0007-1188; 1476-5381
• DOI: 10.1111/j.1476-5381.1992.tb14338.x

1 The effects of β‐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 β‐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 β‐adrenoceptor blockade alone, show that there is an important homeostatic role for the renal sympathetic innervation, mediated by β‐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 β‐adrenoceptor blocking agent will prevent this release. 5 BW B385C (2 mg kg−1), which combines both ACE‐inhibition and β‐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 β‐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 ACE‐inhibition with β‐adrenoceptor blockade.