Effect of yohimbine on renal sympathetic nerve activity and renal norepinephrine spillover in anesthetized rabbits.
The function of presynaptic alpha-2 adrenergic autoinhibition of norepinephrine release was studied in anesthetized rabbits (alfadolone + alfaxalone) with uninterrupted sympathetic impulse traffic. The animals received a tracer infusion of [3H]norepinephrine i.v. Arterial and renal venous concentrations of endogenous norepinephrine and [3H]norepinephrine, the firing rate of the renal sympathetic nerves and renal blood flow were determined. The results were used to calculate the renal fractional [3H]norepinephrine extraction, the renal removal and spillover of norepinephrine, the total body [3H]norepinephrine clearance and total body norepinephrine spillover. Sodium nitroprusside (10-80 micrograms kg-1 min-1 i.v.), which was infused to modulate sympathetic activity through the baroreceptors, caused hypotension and increased the renal sympathetic firing rate and the renal as well as total body norepinephrine spillover. Increases of total body norepinephrine spillover were much higher than increases of renal spillover. Yohimbine (1 mg kg-1 + 0.2 mg kg-1 hr-1 i.v.) caused slight central sympathoexcitation. In addition, it enhanced the renal and total body spillover of norepinephrine at any given firing rate of the renal sympathetic nerves. The distinguishing feature of this study is the measurement of sympathetic firing rate and norepinephrine spillover in one and the same organ, the kidney. The results demonstrate that the alpha-2 adrenergic autoinhibition of norepinephrine release normally operates in the kidney with intact sympathetic impulse traffic. They also suggest its operation in other peripheral sympathetically innervated tissues.
Szabo
B
B
Pharmakologisches Institut der Universität, Freiburg, Federal Republic of Germany.
Schramm
A
A
Starke
K
K
D000758:Anesthesia; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D007668:Kidney / Q000294:innervation* / Q000378:metabolism; D007700:Kinetics; D008297:Male; D009599:Nitroprusside / Q000494:pharmacology; D009638:Norepinephrine / Q000378:metabolism*; D011817:Rabbits; D013564:Sympathetic Nervous System / Q000187:drug effects*; D015016:Yohimbine / Q000494:pharmacology*
D009599:Nitroprusside; D015016:Yohimbine; D009638:Norepinephrine