The action of bombesin on the kidney of the anaesthetized dog.
1. In the anaesthetized dog bombesin had a potent antidiuretic effect, and sometimes arrested urine flow completely. Threshold doses, by i.v. infusion, were of the order of 0.5-1 (ng/kg)/minute. Antidiuresis was the result of a reduction in glomerular filtration rate provoked by a fall in intraglomerular hydrostatic pressure. This, in its turn, was due to afferent vasoconstriction.2. The spasmogenic effect of bombesin on the smooth muscle of the afferent arterioles was directly demonstrated by the radioactive microspheres technique and indirectly by the (85)Kr washout method and by [(3)H]-p-aminohippurate clearance. The vascular compartment most sensitive to bombesin was that of the outer cortical zone, especially in its external half.3. Filtration fraction decreased under the influence of bombesin, indicating that the effect of the polypeptide on postglomerular arterioles was, if present, only of minor importance.4. At high infusion rates (above 6 (ng/kg)/min), bombesin produced a decrease in [(3)H]-p-aminohippurate extraction. The effect of the polypeptide on fractional distal delivery of sodium varied with the dose: at moderate infusion rates it decreased, at high infusion rates it increased. The total glucose appearing in urine following a glucose load was sharply reduced by bombesin. However, the glomerular filtration rate/maximum tubular glucose transport ratio did not show any appreciable change.5. Afferent vasoconstriction produced by bombesin was accompanied by an intense activation of the renin-angiotensin system, as shown by a conspicuous increase in renin secretion, followed by increases in renin activity and angiotensin II concentration in arterial blood. When bombesin was infused into one renal artery only the infused kidney showed afferent vasoconstriction and increased renin secretion. The time-course of renin secretion produced by bombesin depended upon the rate of infusion of the polypeptide. At low rates an increased renin secretion was observed throughout the infusion period, at high rates two peaks of renin secretion could be seen, one at the beginning of the infusion, the other soon after the infusion had finished.6. The mechanism of action of bombesin is discussed and the interest of the polypeptide as a possible hormonal regulator of the circulation and function of the kidney is pointed out.
D000768:Anesthesia, General; D000804:Angiotensin II / Q000097:blood; D000818:Animals; D001001:Anura; D001783:Blood Flow Velocity; D002404:Catheterization; D003404:Creatinine / Q000378:metabolism; D004231:Diuresis / Q000187:drug effects; D004285:Dogs; D005260:Female; D005919:Glomerular Filtration Rate; D005947:Glucose / Q000378:metabolism; D006626:Hippurates / Q000378:metabolism; D007483:Iothalamic Acid / Q000378:metabolism; D007668:Kidney / Q000187:drug effects*; D008297:Male; D008863:Microspheres; D010455:Peptides / Q000494:pharmacology*; D012083:Renin / Q000378:metabolism; D012964:Sodium / Q000032:analysis; D014513:Ureter / Q000187:drug effects; D001743:Urinary Bladder / Q000187:drug effects
D006626:Hippurates; D010455:Peptides; D000804:Angiotensin II; D007483:Iothalamic Acid; D012964:Sodium; D003404:Creatinine; D012083:Renin; D005947:Glucose