Conditions for augmentation of renin release by theophylline.
Isoproterenol, dopamine, glucagon and dibutyryl cyclic AMP (DB-cAMP) increase renin release at low but not at control blood pressure. These findings suggest that autoregulated afferent arteriolar dilation is a prerequisite of renin release mediated by intracellular generation of cyclic AMP. To examine this hypothesis further the effects on renin release of theophylline, which would maintain high intracellular concentration of cAMP by inhibiting phosphodiesterase, were studied in anesthetized dogs. After inhibiting beta-adrenergic stimulation with propranolol, theophylline increased renin release significantly from 0.7 +/- 0.2 to 1.8 +/- 0.7 micrograms/min at control blood pressure and from 23 +/- 4 to 41 +/- 5 micrograms/min at a renal perfusion pressure of about 50 mmHg. The greater effect at low blood pressure occurred despite adjustment of the infusion rate of theophylline to keep arterial plasma concentration of theophylline unaltered. Isoproterenol infusion at low blood pressure raised renin release from 41 +/- 11 to 76 +/- 19 micrograms/min before and 54 +/- 13 to 108 +/- 31 micrograms/min during continuous infusion of theophylline. The renin release response to infusion of theophylline at low blood pressure was not enhanced by DB-cAMP infusion. We conclude that arteriolar dilation provides a condition for stimulation of renin release during the theophylline infusion. Theophylline infusion may augment the effect of isoproterenol on renin release by delaying the intracellular degradation of cAMP.
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D003994:Bucladesine / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D004285:Dogs; D005260:Female; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D012083:Renin / Q000378:metabolism*; D012636:Secretory Rate / Q000187:drug effects; D013806:Theophylline / Q000494:pharmacology*
D010726:Phosphodiesterase Inhibitors; D003994:Bucladesine; D011433:Propranolol; D013806:Theophylline; D000242:Cyclic AMP; D012083:Renin; D007545:Isoproterenol