Increased density of renal amylin binding sites in experimental hypertension.
High-affinity binding sites for the pancreatic beta-cell hormone amylin have been reported in the kidney, and it has been postulated that these sites may be involved in the genesis of hypertension. In the present study, we have used in vivo injection of 125I-amylin and in vitro autoradiographic techniques to assess renal amylin binding in both a genetic and a surgically induced model of hypertension. In the spontaneously hypertensive rat (SHR) at 6 weeks of age, before the rise in systolic blood pressure, there was a 36% increase in density of amylin binding compared with their normotensive counterpart, the Wistar-Kyoto rat (WKY). In SHR, there was a further increase in the density of amylin binding (to 53% greater) as the systolic blood pressure rose between 6 and 12 weeks of age. Histological examination of kidneys from SHR at 12 weeks of age revealed staining for a brush border glycoprotein, normally restricted to the proximal tubules, extending from the urinary pole into half of the epithelial lining of the glomerular capsule. In contrast to WKY, these cells also bound 125I-amylin with high density in SHR. In a rat model of renal ablation and hypertension, systolic blood pressure correlated with the density of 125I-amylin binding in the renal cortex (r=.54, P=.003, n=28). The changes in amylin binding reported here suggest a possible role for this peptide and/or activation of its receptor in the genesis as well as the maintenance of hypertension.
Wookey
P J
PJ
Department of Medicine, University of Melbourne, Austin and Repatriation Medical Centre, Repatriation Campus, Victoria, Australia. wookey@austin.unimelb.edu.au
Cao
Z
Z
van Geenen
R C
RC
Voskuil
M
M
Darby
I A
IA
Komers
R
R
Cooper
M E
ME
D000682:Amyloid / Q000378:metabolism*; D000818:Animals; D001345:Autoradiography; D001665:Binding Sites; D006973:Hypertension / Q000378:metabolism* / Q000473:pathology; D058228:Islet Amyloid Polypeptide; D007668:Kidney / Q000378:metabolism* / Q000473:pathology; D008297:Male; D009392:Nephrectomy; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D017207:Rats, Sprague-Dawley; D014018:Tissue Distribution
D000682:Amyloid; D058228:Islet Amyloid Polypeptide