Pindolol increases plasma norepinephrine concentration by stimulation of beta 2-adrenoceptors in conscious spontaneously hypertensive rats.
The beta-adrenoceptor antagonist pindolol [10-1,000 micrograms/kg subcutaneously (s.c.)] caused dose-related decreases in mean arterial pressure (MAP) and increased heart rate (HR) in conscious spontaneously hypertensive rats (SHR). The lowest dose of pindolol (10 micrograms/kg) decreased MAP by 25 mm Hg (-16%) without affecting plasma norepinephrine (NE) or plasma renin concentration (PRC). However, higher doses of pindolol elicited dose-related increases in plasma NE concentration and PRC. Plasma epinephrine concentration was not altered by pindolol. The selective beta 2-adrenoceptor antagonist ICI 118,551 (3 mg/kg, s.c.) prevented the tachycardia but not the increase in PRC caused by 100 micrograms/kg pindolol. Treatment with ICI 118,551 completely eliminated the 45% increase in plasma NE elicited by 100 micrograms/kg of pindolol even though the decrease in MAP caused by this dose of pindolol was the same in the presence (-33 mm Hg) and absence (-34 mm Hg) of beta 2-adrenoceptor blockade. These results indicate that the vasodepressor action of pindolol in SHR does not result from an agonistic effect at postjunctional beta 2-adrenoceptors in the vasculature. In addition, the increases in plasma NE concentration produced by pindolol result from stimulation of beta 2-adrenoceptors. These beta 2-adrenoceptors may be located prejunctionally on sympathetic neurons.
Department of Pharmacology, University of Texas Health Science Center, San Antonio 78284-7764.
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Keeton
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006339:Heart Rate / Q000187:drug effects; D006973:Hypertension / Q000503:physiopathology*; D008297:Male; D009638:Norepinephrine / Q000097:blood*; D010869:Pindolol / Q000008:administration & dosage / Q000494:pharmacology*; D011412:Propanolamines / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D011943:Receptors, Adrenergic, beta / Q000187:drug effects* / Q000502:physiology; D012083:Renin / Q000097:blood
D000319:Adrenergic beta-Antagonists; D011412:Propanolamines; D011943:Receptors, Adrenergic, beta; C026777:ICI 118551; D010869:Pindolol; D012083:Renin; D009638:Norepinephrine