ISSN:
1432-0428
Keywords:
Prostaglandins
;
angiotensin
;
sodium-lithium countertransport
;
hypertension
;
diabetic nephropathy
Source:
Springer Online Journal Archives 1860-2000
Topics:
Medicine
Notes:
Summary 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 4ng·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〈0.01), in hypertensive patients with normal sodium-lithium countertransport activity in erythrocytes (−8% p〈0.01) in hypertensive patients with high sodium-lithium countertransport (−6% p〈0.01) and in hypertensive microalbuminuric patients (−5% p〈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. An inverse relation was found between angiotensin II-induced decrease in the glomerular filtration rate and the sodium-lithium countertransport activity in erythrocytes during indomethacin treatment. Hypertensive and microalbuminuric patients with a sodium-lithium countertransport activity higher than 0.41 mmol·l erythrocyte−1·h−1 (the upper limit in normal subjects) also had a greater intimal plus medial thickness of the carotid artery using an ultrasonic imaging technique. Chronic indomethacin administration (30 days) significantly decreased the baseline overnight fasting glomerular filtration rate in normotensive and in hypertensive patients with normal but not in hypertensive and microalbuminuric patients with high sodium-lithium countertransport activity. In conclusion these results demonstrate that: (1) excessive synthesis of vasodilatory prostaglandins antagonizes the regulation of renal haemodynamics by angiotensin II, at least partially accounting for hyperfiltration in Type 1 diabetes, (2) elevated sodium-lithium countertransport activity in erythrocytes identifies a subgroup of patients with Type 1 diabetes and hypertension, with and without microalbuminuria, in whom the normalization of urinary excretion rate of prostaglandins does not restore a normal response to angiotensin II.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/BF00400280
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