The role of prostaglandins in the alpha- and beta-adrenoceptor mediated renin release response to graded renal nerve stimulation.

The role of prostaglandins in the renin release response to renal nerve stimulation (RNS) at different intensities was examined in the anaesthetized dog. The animals were divided into two groups receiving either low or high level RNS, defined by the frequencies of stimulation producing reduction in renal blood flow by 5% or less and 50%. Indomethacin or diclofenac sodium (5 mg/kg i.v.), prostaglandin synthesis inhibitors, did not affect the renin release response to low level RNS but decreased the renin release response to high level RNS by 31 +/- 8% (P less than 0.01). Addition of metoprolol, (0.5 mg/kg i.v.) beta-1-adrenoceptor antagonist, to indomethacin or diclofenac sodium resulted in a greater reduction (68 +/- 6% P less than 0.01) of the renin release response to high level RNS compared to that produced by either drug alone. Metoprolol, alone, reduced the renin release response to high level RNS by 37 +/- 14% (P less than 0.05). Phenoxybenzamine (0.6 microgram . kg-1 . min-1), alpha-adrenoceptor antagonist, into the renal artery practically abolished the renal vasoconstrictor response to high level RNS and reduced the renin release response by 50 +/- 7% (P less than 0.01). Addition of metoprolol to phenoxybenzamine practically abolished the renal vasoconstrictor response and the renin release response to high level RNS; 94 +/- 4% (P less than 0.01). Addition of phenoxybenzamine to indomethacin or diclofenac sodium practically abolished the renal vasoconstrictor response to high level RNS but did not produce any greater reduction of the renin release response than that produced by either drug alone. These findings suggest that low level RNS results in renin release which is not dependent on prostaglandins. High level RNS results in renin release which is partly mediated by beta-1-adrenoceptors and partly related to alpha-adrenoceptors mediated renal vasoconstriction. Prostaglandins are not involved in the renin release deriving from alpha-adrenoceptor mediated renal vasoconstriction.