Antihypertensive effects of 12 beta adrenoceptor antagonists in conscious spontaneously hypertensive rats: relationship to changes in plasma renin activity, heart rate and sympathetic nerve function.
Twelve beta adrenoceptor antagonists were examined for their effects on mean blood pressure (MBP), heart rate (HR), plasma renin activity (PRA) and sympathetic nerve function in spontaneously hypertensive rats (SHR). The selected drugs included cardioselective agents (acebutolol, atenolol and metoprolol), agents with intrinsic sympathomimetic activity (oxprenolol, acebutolol, alprenolol and pindolol) and agents with local anesthetic activity (propranolol, oxprenolol, acebutolol, alprenolol and labetalol). All 12 beta adrenoceptor antagonists, administered once daily for 4 days (30 mg/kg p.o.), significantly decreased MBP of SHR. This reduction in MBP was dissociable from both reductions in HR as well as peripheral beta adrenoceptor blockade. In addition, the onset of MBP reduction was slower than the onset of beta adrenoceptor blockade and became greater with duration of treatment. PRA activity was significantly and markedly reduced by both bunolol and metoprolol shortly after dosing at a time when HR was significantly reduced but MBP was not. Conversely, at a time when MBP was significantly reduced by both bunolol and metoprolol, PRA and HR were found to be normal. The changes in HR and PRA were correlated with peripheral beta adrenoceptor blockade but changes in MBP were not. Bunolol, metoprolol and propranolol had no consistent inhibitory effect on pressor responses to nerve stimulation in pithed SHR, although positive chronotropic responses to norepinephrine, tyramine, dimethylphenylpiperazinium and angiotensin I and II were significantly and markedly reduced. It is concluded that beta adrenoceptor antagonists, as a class, reduce MBP of conscious SHR, provided that sufficient time is allowed for this observation to occur. Furthermore, the reduction in MBP caused by beta adrenoceptor antagonists is unrelated to acute beta adrenoceptor blockade, changes in HR, reductions in PRA or inhibition of sympathetic nerve function. Finally, cardioselectivity, intrinsic sympathomimetric activity and local anesthetic activity are not required for the antihypertensive activity of these agents.
Antonaccio
M J
MJ
High
J
J
DeForrest
J M
JM
Sybertz
E
E
D000070:Acebutolol / Q000627:therapeutic use; D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use*; D000779:Anesthetics, Local; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D003655:Decerebrate State; D006321:Heart / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D006973:Hypertension / Q000188:drug therapy*; D007545:Isoproterenol / Q000494:pharmacology; D002040:Levobunolol / Q000627:therapeutic use; D008297:Male; D008790:Metoprolol / Q000627:therapeutic use; D010096:Oxprenolol / Q000627:therapeutic use; D011433:Propranolol / Q000627:therapeutic use; D051381:Rats; D011918:Rats, Inbred SHR; D012083:Renin / Q000097:blood*; D013564:Sympathetic Nervous System / Q000187:drug effects*; D013566:Sympathomimetics / Q000627:therapeutic use; D013997:Time Factors
D000319:Adrenergic beta-Antagonists; D000779:Anesthetics, Local; D013566:Sympathomimetics; D010096:Oxprenolol; D000070:Acebutolol; D011433:Propranolol; D012083:Renin; D002040:Levobunolol; D008790:Metoprolol; D007545:Isoproterenol