Comparison of glomerular and mesangial prostaglandin synthesis and glomerular contraction in two rat models of diabetes mellitus.
Enhanced prostaglandin production is postulated to contribute to altered vascular reactivity and glomerular hyperfiltration in early insulin-deficient diabetes mellitus. Rats with streptozocin-induced diabetes (STZ-D) show glomerular hyperfiltration and develop renal disease. BB rats with genetic diabetes (BB-D) also hyperfilter but have only minor renal lesions. We therefore compared glomerular and mesangial prostaglandin E2 (PGE2) production and glomerular contractility in response to pressors as a reflection of in vitro vascular reactivity in these models. Glomeruli isolated from rats with 3 wk of STZ-D produced significantly more PGE2 under basal and ionophore A23187-stimulated conditions than those from control rats. Glomeruli from BB-D rats under basal and stimulated conditions, however, generated amounts of PGE2 that were comparable to either those of nondiabetic littermates or of normal Wistar rats. Mesangial cells cultured from glomeruli of STZ-D, BB-D, and control rats all had identical prostaglandin profiles judged by conversion of [14 C]arachidonic acid. They also produced comparable amounts of PGE2 under basal conditions and after stimulation with angiotensin II or A23187, as determined by radioimmunoassay. Planar surface area of glomeruli isolated from control rats showed a dose-dependent decrease in response to angiotensin II (10(-11)-10(-9) M). This response to angiotensin II was at least as great in glomeruli from STZ-D rats. Contraction of glomeruli from control and STZ-D rats was also comparable after vasopressin or norepinephrine. Similarly, glomeruli from BB-D and BB control rats contracted in a comparable fashion to angiotensin II and norepinephrine.(ABSTRACT TRUNCATED AT 250 WORDS)
D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism; D001127:Arginine Vasopressin / Q000494:pharmacology; D000001:Calcimycin / Q000494:pharmacology; D002478:Cells, Cultured; D003921:Diabetes Mellitus, Experimental / Q000473:pathology / Q000503:physiopathology*; D015232:Dinoprostone; D007678:Kidney Glomerulus / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology; D011458:Prostaglandins E / Q000096:biosynthesis*; D051381:Rats; D011913:Rats, Inbred BB; D011919:Rats, Inbred Strains; D012016:Reference Values
D001095:Arachidonic Acids; D011458:Prostaglandins E; D000804:Angiotensin II; D001127:Arginine Vasopressin; D016718:Arachidonic Acid; D000001:Calcimycin; D015232:Dinoprostone; D009638:Norepinephrine