Congestive heart failure in diabetes with hypertension may be due to uncoupling of the atrial natriuretic peptide receptor-effector system in the kidney basolateral membrane.
Hypertension is known to potentiate the risk of congestive heart failure (CHF) in diabetic individuals. Receptor-effector systems for atrial natriuretic peptide (ANP), which is known to regulate intracellular calcium (Ca2+), were studied in the kidney during hypertensive-diabetic cardiomyopathy in rats. Animals were divided into four groups: control, diabetic (D), hypertensive (H), and diabetic plus hypertensive (D + H). Diabetes was induced by a streptozotocin (65 mg/kg) injection and hypertension was induced by abdominal aortic constriction; studies were done at 1 and 6 weeks. Plasma ANP was increased at 1 week in the D, H, and D + H groups. There was a significant increase in the activity of Ca2+ + magnesium (Mg2+) adenosine triphosphatase (ATPase), which acts as a Ca2+ pump, in the kidney basolateral membrane from D, H, and D + H group at the 1 week study. Ca2+ + Mg2+ ATPase, on the other hand, was significantly decreased in the D + H group only at 6 weeks. This was associated with a decrease in plasma ANP, an increase in the kidney ANP receptor number, and a decrease in guanylate cyclase activity. The response of the Ca2+ pump to ANP was also attenuated. Since ANP is known to mediate its cellular effects in part by increasing Ca2+ + Mg2+ ATPase, the observed changes in the D + H group may contribute to the development of nephropathy and CHF.
Sahai
A
A
Department of Anatomy, St. Boniface General Hospital Research Centre, Faculty of Medicine, University of Manitoba, Winnipeg, Canada.
Ganguly
P K
PK
D000818:Animals; D009320:Atrial Natriuretic Factor / Q000097:blood / Q000378:metabolism*; D001693:Biological Transport, Active; D017301:Ca(2+) Mg(2+)-ATPase / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D000252:Calcium-Transporting ATPases / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000150:complications* / Q000378:metabolism; D006333:Heart Failure / Q000209:etiology*; D006973:Hypertension / Q000097:blood / Q000150:complications* / Q000378:metabolism; D007672:Kidney Cortex / Q000378:metabolism*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D017461:Receptors, Atrial Natriuretic Factor; D011956:Receptors, Cell Surface / Q000097:blood / Q000378:metabolism*
D011956:Receptors, Cell Surface; D009320:Atrial Natriuretic Factor; D017301:Ca(2+) Mg(2+)-ATPase; D017461:Receptors, Atrial Natriuretic Factor; D000252:Calcium-Transporting ATPases; D002118:Calcium