Activation of beta 2-adrenoceptors by isoprenaline and adrenaline enhances noradrenaline release in cortical kidney slices of young spontaneously hypertensive rats.
The aim of the present study was to investigate beta-adrenoceptor modulation of noradrenaline release from sympathetic nerves in superfused cortical kidney slices of 4-week-old spontaneously hypertensive rats (SHR) and age-matched controls (WKY). After preincubation with 3H-noradrenaline the kidney slices were electrically stimulated in superfusion chambers. The stimulation induced (S-I) outflow of radioactivity was mainly composed of unmetabolized 3H-noradrenaline in both strains and thus taken as an index of noradrenaline release. There was a frequency-dependent (1.25-20 Hz) increase in the S-I outflow of radioactivity. At all stimulation frequencies tested S-I outflow of radioactivity was similar or even slightly lower in SHR than in WKY kidney slices in either the absence or presence of cocaine (10 mumol/l). The non-selective beta-adrenoceptor agonists isoprenaline (0.1 mumol/l) and adrenaline (0.01 and 0.1 mumol/l) enhanced S-I outflow of radioactivity. The facilitatory effects of isoprenaline (0.1 mumol/l) and adrenaline (0.1 mumol/l) were blocked by the selective beta 2-adrenoceptor antagonist ICI 118551 (0.1 mumol/l) but not by the selective beta 1-adrenoceptor antagonist atenolol (0.3 mumol/l). The cell-permeable cAMP analogue 8-bromo-cAMP (300 mumol/l) enhanced S-I outflow of radioactivity to a similar extent in both SHR and WKY kidney slices. A combination of 8-bromo-cAMP (300 mumol/l) and adrenaline (0.1 mumol/l) did not enhance S-I outflow of radioactivity to a greater extent than 8-bromo cAMP (300 mumol/l) alone in both strains.(ABSTRACT TRUNCATED AT 250 WORDS)
Medizinische Universitätsklinik Freiburg, Innere Medizin IV, Federal Republic of Germany.
L C
LC
Rump
M J
MJ
Schuster
P
P
Schollmeyer
D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D004558:Electric Stimulation; D004837:Epinephrine / Q000494:pharmacology*; D006973:Hypertension / Q000378:metabolism*; D007545:Isoproterenol / Q000494:pharmacology*; D007672:Kidney Cortex / Q000187:drug effects* / Q000378:metabolism; D009638:Norepinephrine / Q000378:metabolism*; D051381:Rats; D011918:Rats, Inbred SHR; D011919:Rats, Inbred Strains; D011921:Rats, Inbred WKY; D011943:Receptors, Adrenergic, beta / Q000187:drug effects* / Q000378:metabolism; D013564:Sympathetic Nervous System / Q000187:drug effects
D000319:Adrenergic beta-Antagonists; D011943:Receptors, Adrenergic, beta; D015124:8-Bromo Cyclic Adenosine Monophosphate; D007545:Isoproterenol; D009638:Norepinephrine; D004837:Epinephrine