Impaired response to angiotensin II in type 1 (insulin-dependent) diabetes mellitus. Role of prostaglandins and sodium-lithium countertransport activity.
The pathogenesis of diabetic nephropathy remains elusive. A role for renal prostaglandins in antagonizing the hormonal effects of renin-angiotensin II has been postulated as a putative factor leading to hyperfiltration in patients with Type 1 (insulin-dependent) diabetes mellitus. Our aim was to elucidate the effects of angiotensin II on kidney haemodynamics and on blood pressure in eight normal subjects, in nine normotensive, in nine hypertensive with normal sodium-lithium countertransport activity in erythrocytes, in seven hypertensive without and in eight hypertensive Type 1 diabetic patients with microalbuminuria and with high sodium-lithium countertransport activity in erythrocytes. Angiotensin II infusion (4 ng.kg-1.min-1 for 60 min) decreased the glomerular filtration rate to a greater extent in normal subjects (-20%), than in normotensive patients (-5% p less than 0.01), in hypertensive patients with normal sodium-lithium countertransport activity in erythrocytes (-8% p less than 0.01) in hypertensive patients with high sodium-lithium countertransport (-6% p less than 0.01) and in hypertensive microalbuminuric patients (-5% p less than 0.01) with Type 1 diabetes. The urinary excretion rate of vasodilatory prostaglandins was two-three fold higher in all patients than in normal subjects. Acute indomethacin treatment restored a normal response to angiotensin II infusion in normotensive patients, but did not change the renal haemodynamic response in normal subjects. With regard to hypertensive patients with and without microalbuminuria indomethacin treatment restored a normal response to angiotensin II in some but not all patients.(ABSTRACT TRUNCATED AT 250 WORDS)
Fioretto
P
P
Instituto di Medicina Interna, Padova, Italy.
Sambataro
M
M
Cipollina
M G
MG
Duner
E
E
Giorato
C
C
Morocutti
A
A
Mollo
F
F
Ben
G P
GP
Carraro
A
A
Sacerdoti
D
D
D000328:Adult; D000419:Albuminuria; D000804:Angiotensin II / Q000494:pharmacology*; D017920:Antiporters; D001794:Blood Pressure / Q000187:drug effects; D002352:Carrier Proteins / Q000097:blood*; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000503:physiopathology*; D004912:Erythrocytes / Q000378:metabolism; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006801:Humans; D006973:Hypertension / Q000097:blood / Q000150:complications / Q000503:physiopathology*; D007213:Indomethacin / Q000494:pharmacology*; D008297:Male; D011188:Potassium / Q000652:urine; D011453:Prostaglandins / Q000502:physiology*; D012016:Reference Values; D012079:Renal Circulation / Q000187:drug effects; D012964:Sodium / Q000652:urine; D014655:Vascular Resistance / Q000187:drug effects
D017920:Antiporters; D002352:Carrier Proteins; D011453:Prostaglandins; C045885:sodium-lithium countertransporter; D000804:Angiotensin II; D012964:Sodium; D011188:Potassium; D007213:Indomethacin