Amylin induces natriuresis by a central angiotensin-dependent mechanism.
This study provides evidence that amylin acts centrally to increase sodium excretion in the sheep. Amylin was infused at 8 mg/h into a carotid artery (IC), via a lateral ventricle (ICV), intravenously (IV) or intra-renally (IR) into conscious sheep (n=5 per group). Renal sodium excretion increased by at least 3-fold after 1 h of amylin infusion by ICV (66+/-14 to 367+/-35 mmol/min) and IC (78+/-14 to 244+/-22 mmol/min) routes of administration. Amylin infusion IV caused a 1.5-fold increase in sodium excretion while IR infusion did not have a significant effect. The natriuretic effect of ICV infused amylin was blocked by pre-treatment with the angiotensin AT1 receptor antagonist, losartan (1 mg/h). No changes in blood pressure or heart rate were recorded at this dose of amylin by any route of administration. Plasma renin concentration increased (1.32+/-0.22 to 2.55+/-0.73 pmol/Ang I/h; P<0.05) following IR infusion of amylin, and remained unchanged when amylin was infused by the other routes of administration. We conclude that amylin causes changes in sodium excretion in sheep through a central, angiotensin-dependent pathway and that amylin may increase renin secretion by a direct effect on the kidney.
Mathai
M L
ML
Howard Florey Institute of Experimental Physiology and Medicine University of Melbourne, Victoria 3010, Australia. mlm@hfi.unimelb.edu.au
Sosa Leon
L A
LA
May
C N
CN
Thomson
C E
CE
McKinley
M J
MJ
D000682:Amyloid / Q000737:chemistry* / Q000502:physiology; D000809:Angiotensins / Q000378:metabolism*; D000818:Animals; D001794:Blood Pressure; D002241:Carbohydrates / Q000737:chemistry; D002339:Carotid Arteries / Q000473:pathology; D004573:Electrolytes; D005260:Female; D006339:Heart Rate; D058228:Islet Amyloid Polypeptide; D007668:Kidney / Q000378:metabolism; D019808:Losartan / Q000378:metabolism / Q000494:pharmacology; D009318:Natriuresis; D044140:Receptor, Angiotensin, Type 1 / Q000737:chemistry; D012083:Renin / Q000097:blood / Q000378:metabolism; D012756:Sheep; D012964:Sodium / Q000378:metabolism / Q000652:urine; D013997:Time Factors
D000682:Amyloid; D000809:Angiotensins; D002241:Carbohydrates; D004573:Electrolytes; D058228:Islet Amyloid Polypeptide; D044140:Receptor, Angiotensin, Type 1; D012964:Sodium; D012083:Renin; D019808:Losartan