CARDIOVASCULAR AND RENAL EFFECTS OF ALPHA-TRINOSITOL IN ISCHEMIC HEART-FAILURE RATS

Previous studies have demonstrated that alpha-trinositol (D-myo-inosit ol-1.2.6-trisphosphate; PP56) may act as a functional neuropeptide Y ( NPY) inhibitor. Because NPY is known to be a potent vasoconstrictor, t he effects of alpha-trinositol on renal function, vascular responses a nd the potentiating effects of NPY were investigated in rats with cong estive heart failure (CHF) induced by ligation of the left coronary ar tery. Incremental doses of alpha-trinositol were given to conscious ra ts (bolus 2, 4 or 10 mg/kg i.v. followed by a 15-minute infusion 20, 4 0 and 100 mg/kg/h, respectively). Urinary volume, sodium and potassium excretions were significantly increased in both CHF and sham-operated control animals after alpha-trinositol administration compared with s aline. Diuresis and natriuresis were observed also during co-administr ation of alpha-trinositol with NPY but not with norepinephrine (NE). I n the pithed CHF rats, threshold doses of NPY potentiated the presser effects of endothelin-1 (ET-1) and angiotensin II (AII), but not prega nglionic nerve stimulation or phenylephrine administration. Alpha-trin ositol antagonized both the presser response to NPY and the potentiati on by NPY of presser responses to effects of ET-1 and AII. Our data sh ow that alpha-trinositol exhibis diuretic and natriuretic effects as w ell as vascular antagonistic effects on NPY in normal and CHF rats. Th ese effects of alpha-trinositol may be due to an interaction with NPY mediated antidiuresis and antinatriuresis.