The expression of the glomerular receptor for angiotensin II (Ang II-R) was examined longitudinally following the induction of anti-glomerular basement membrane (GBM) nephritis in the rat. The specific aim of the project was to determine whether immunologically-induced glomerular injury led to significant abnormalities of the relationship between glomerular Ang II-R and its circulating ligand, Ang II. Scatchard analysis was used to measure Ang II-R on purified glomeruli at selected time intervals over two months following a single dose of sheep anti-rat GBM antibody. Corresponding values for plasma Ang II were determined. Receptor density fell to approximately 50% by 16 hours following the injection of antibody (control 96.4 +/- 9.3 x 10(6); nephritic 52.6 +/- 5.6 x 10(6) receptors/glomerulus; P less than 0.001) and there was a corresponding threefold increase in plasma Ang II (control 21.0 +/- 2.5; nephritic 66.6 +/- 20.6 pg/ml; P less than 0.01). However, this reduction in receptor binding could not be explained by the rise in plasma Ang II concentration, as effective blockade of the RAS by enalapril did not alter receptor expression (56.1 +/- 4.6 x 10(6) receptors/glomerulus). Subsequently, a rise in receptor density and a corresponding fall in plasma Ang II were observed: three days after antibody administration, receptor concentration had increased significantly above control values (150.5 +/- 11.9 x 10(6] while plasma Ang II was undetectable (that is, less than 5 pg/ml). Ang II-R remained elevated for the next two weeks but returned to normal four to eight weeks after the administration of nephrotoxic antibody.(ABSTRACT TRUNCATED AT 250 WORDS)
Abstract. Experimental studies demonstrate impaired regulation of the mesangial angiotensin I1 (AII) receptor in diabetes. This could contribute to the disturbance of glomerular blood flow and the development of diabetic nephropathy. The aim of this study was to determine whether a similar receptor abnormality occurs in patients with type I insulin-dependent diabetes mellitus (IDDM) and if so whether this is more prevalent in patients with micro-or macro-albuminuria. The platelet A11 receptor was chosen because of its availability from the circulation and its comparable regulatory properties to tissue-based receptors. The interaction between plasma All and its platelet receptor was examined in 45 patients with TDDM and 36 age-and sex-matched control subjects. Seven patients had clinical nephropathy and two had persistent micro-albuminuria. The duration of diabetes varied from 1 month to 42 years.There was a significant inverse correlation between plasma AIT and the logarithm of receptor number in the control group ( r = -0.555, P<0.001). This relationship was not observed in the diabetic patients irrespective of the duration of disease or the presence of nephropathy. Receptor expression in patients without nephropathy showed no correlation with either duration of disease or the degree of glycaemic control. However, a significant relationship between AT1 receptor number and duration of diabetes was noted in the group with nephropathy (r = 0.723, P < 0.05). Patients without nephropathy had a significantly lower receptor number than control subjects (i.e. 3.9k0.4 and 5.1 kO.7 sites per cell respectively; P=0.02), while comparable values to controls were observed in patients with renal disease (5.7-l 1.2 sites per cell). Plasma renin and A11 levels for both groups ofpatients were comparable to those observed in the control subjects.If these findings are representative of tissue-based A11 receptors, then the loss of ligand/receptor relationship in the presence of higher receptor expression in patients with nephropathy could provide an explana- tion for the glomerular haemodynamic abnormalities observed in human diabetes.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.