Cardiovascular and renal effects of alpha-trinositol in ischemic heart failure rats.
Previous studies have demonstrated that alpha-trinositol (D-myo-inositol-1.2.6-trisphosphate; PP56) may act as a functional neuropeptide Y (NPY) inhibitor. Because NPY is known to be a potent vasoconstrictor, the effects of alpha-trinositol on renal function, vascular responses and the potentiating effects of NPY were investigated in rats with congestive heart failure (CHF) induced by ligation of the left coronary artery. Incremental doses of alpha-trinositol were given to conscious rats (bolus 2, 4 or 10 mg/kg i.v. followed by a 15-minute infusion 20, 40 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 saline. Diuresis and natriuresis were observed also during co-administration of alpha-trinositol with NPY but not with norepinephrine (NE). In the pithed CHF rats, threshold doses of NPY potentiated the pressor effects of endothelin-1 (ET-1) and angiotensin II (AII), but not preganglionic nerve stimulation or phenylephrine administration. Alpha-trinositol antagonized both the pressor response to NPY and the potentiation by NPY of pressor responses to effects of ET-1 and AII. Our data show that alpha-trinositol exhibis diuretic and natriuretic effects as well as vascular antagonistic effects on NPY in normal and CHF rats. These effects of alpha-trinositol may be due to an interaction with NPY mediated antidiuresis and antinatriuresis.
Sun
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Department of Pharmacology, University of Göteborg, Sweden.
Feng
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QP
Zhao
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Edvinsson
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Hedner
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T
D000818:Animals; D002319:Cardiovascular System / Q000187:drug effects*; D004231:Diuresis / Q000187:drug effects; D006333:Heart Failure / Q000188:drug therapy / Q000503:physiopathology*; D006439:Hemodynamics / Q000187:drug effects; D007295:Inositol Phosphates / Q000494:pharmacology*; D007668:Kidney / Q000187:drug effects*; D008297:Male; D017202:Myocardial Ischemia / Q000503:physiopathology*; D009318:Natriuresis / Q000187:drug effects; D009478:Neuropeptide Y / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley
D007295:Inositol Phosphates; D009478:Neuropeptide Y; C059368:atrinositol