title: Picotamide, a dual TXB synthetase inhibitor and TXB receptor antagonist, reduces exercise-induced albuminuria in microalbuminuric patients with NIDDM.
abstract: We investigated the short-term effect of the TXB inhibitor picotamide on albuminuria induced by exercise in 15 microalbuminuric (i.e., with UAE at rest between 20 and 200 micrograms/min) type II diabetic patients (12 men and 3 women, age 56 +/- 2, BMI 28 +/- 1 kg/m2) and in six normal age-matched control subjects. The diabetic subjects performed five submaximal exercise tests (90% of theoretical heart rate) on a cycle ergometer: the first two under basal conditions; the third and fifth after subjects had received picotamide (900 mg/day) or placebo (3 tablets/day) for 10 days; the fourth exercise always was performed after 10 days of wash-out. Control subjects performed two exercises: the first in baseline conditions and the second after 10 days of picotamide administration (900 mg/day). When diabetic patients were untreated, a significant (P < 0.05) increase in UAE with respect to baseline levels was observed immediately after and 1 h after the exercise test. After picotamide administration, UAE significantly decreased (P < 0.05) immediately after and 1 h after exercise, as compared with diabetic patients given a placebo. In normal subjects, exercise was followed by a slight increase in UAE, which was not significantly affected by picotamide administration. Our results show that short-term administration of picotamide is associated with a reduction in UAE after exercise in type II diabetes patients with microalbuminuria while at rest. Picotamide, a TXB synthetase and receptor inhibitor, may decrease exercise-induced albuminuria in diabetic patients through a reduction in circulating TXB levels and inhibition of TXB action, which in turn may act by lowering glomerular capillary hydraulic pressure.
authors.affiliation: Cattedra di Clinica Medica, University of Brescia, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Giustina
authors.forename: S
authors.initials: S
authors.lastname: Bossoni
authors.forename: A
authors.initials: A
authors.lastname: Cimino
authors.forename: M T
authors.initials: MT
authors.lastname: Comini
authors.forename: N
authors.initials: N
authors.lastname: Gazzoli
authors.forename: G B
authors.initials: GB
authors.lastname: Leproux
authors.forename: W B
authors.initials: WB
authors.lastname: Wehrenberg
authors.forename: G
authors.initials: G
authors.lastname: Romanelli
authors.forename: G
authors.initials: G
authors.lastname: Giustina
mesh_terms: D000419:Albuminuria / Q000517:prevention & control*; D001794:Blood Pressure; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000503:physiopathology* / Q000652:urine; D015444:Exercise; D005260:Female; D006442:Glycated Hemoglobin / Q000032:analysis; D006339:Heart Rate; D006801:Humans; D008297:Male; D008875:Middle Aged; D010795:Phthalic Acids / Q000494:pharmacology*; D005082:Physical Exertion; D017482:Receptors, Thromboxane / Q000037:antagonists & inhibitors*; D012016:Reference Values; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors*; D013997:Time Factors
chemical_list: D006442:Glycated Hemoglobin; D010795:Phthalic Acids; D017482:Receptors, Thromboxane; D013930:Thromboxane-A Synthase; C011581:picotamide