Adrenaline as an endogenous agonist for presynaptic beta-adrenoceptors and their relevance to the development of hypertension in spontaneously hypertensive rats.
We attempted to identify an endogenous agonist for presynaptic facilitatory beta-adrenoceptors. Pulmonary arteries isolated from guinea pigs 5 days after bilateral adrenalectomy and renal arteries from 4-week-old spontaneously hypertensive rats (SHR) exposed to swimming stress for 1 h were preloaded with 3H-noradrenaline and superfused with Krebs medium. Electrical field stimulation was carried out four times at 15-min intervals (S1 to S4). Beta-antagonist carteolol at 10(-8), 10(-7) and 10(-6) mol/l was cumulatively applied after S1, S2 and S3 and the effect was estimated as the evoked 3H release ratio, Sx:S1. Catecholamine contents in arteries were measured by high performance liquid chromatography with electron capture. In sham-operated pulmonary arteries, carteolol inhibited evoked 3H release in a concentration-dependent manner. This inhibition was completely abolished by adrenalectomy. Adrenalectomy depleted adrenaline contents without modification of noradrenaline and dopamine. In renal arteries, swimming stress potentiated carteolol-induced concentration-dependent inhibition of evoked 3H release and increased adrenaline and dopamine contents without modification of noradrenaline. Adrenaline derived from adrenals and probably stored and coreleased with noradrenaline acts as an endogenous agonist for presynaptic beta-adrenoceptors.
Misu
Y
Y
Department of Pharmacology, Yokohama City University School of Medicine, Japan.
Kuwahara
M
M
Amano
H
H
Kubo
T
T
D000818:Animals; D002354:Carteolol / Q000494:pharmacology; D004837:Epinephrine / Q000502:physiology*; D006168:Guinea Pigs; D006973:Hypertension / Q000503:physiopathology*; D008024:Ligands; D008297:Male; D051381:Rats; D011918:Rats, Inbred SHR / Q000502:physiology*; D011919:Rats, Inbred Strains / Q000502:physiology*; D011943:Receptors, Adrenergic, beta / Q000502:physiology*
D008024:Ligands; D011943:Receptors, Adrenergic, beta; D002354:Carteolol; D004837:Epinephrine