EFFECTS OF CHRONIC INFUSIONS OF ALPHA-TRINOSITOL ON REGIONAL AND CARDIAC HEMODYNAMICS IN CONSCIOUS RATS

1 Male, Long Evans rats (350-450 g) were chronically instrumented for the measurement of renal, mesenteric and hindquarters haemodynamics, a nd were given three consecutive, 24 h infusions of vehicle (sterile sa line at 0.3 ml h(-1); n = 8) or alpha-trinositol (D-myo-inositol-1,2,6 -triphosphate) at 5, 20 and 80 mg kg(-1) h(-1) (0.3 ml h(-1) n = 9). D uring infusion of alpha-trinositol at 5 or 20 mg kg(-1) h(-1), cardiov ascular changes were little different from those seen during saline in fusion. However, during infusion of alpha-trinositol at 80 mg kg(-1) h (-1) there were increases in hindquarters vascular conductance, renal flow and vascular conductance, that were all significantly different f rom the changes seen in the saline group. Infusion of alpha-trinositol at the high dose in naive rats (n = 8) had even more marked vasodilat or effects. 2 Two groups of rats (n = 8 in each), chronically instrume nted for the measurement of cardiac haemodynamics, were given 48 h inf usions of saline (0.3 ml h(-1)) or alpha-trinositol (2 mg kg(-1) bolus , 80 mg kg(-1) h(-1) infusion at 0.3 ml h(-1)). During the infusion of saline, there were slight reductions in heart rate, cardiac index, pe ak aortic flow, dF/dt(max) and central venous pressure. fn the animals receiving alpha-trinositol, with the exception of central venous pres sure, all the above variables, together with total peripheral conducta nce, increased. 3 These results, collectively, indicate that increment al infusions of alpha-trinositol do not reveal its full vasodilator po tential, possibly due to concurrent activation of counter-regulatory v asoconstrictor mechanisms. However, infusion of alpha-trinositol at a high dose causes substantial increases in renal, mesenteric and hindqu arters flows and vascular conductances, supported by significant incre ases in indices of cardiac inotropism. Such effects, in the absence of significant hypotension, tachycardia or signs of desensitization, giv e alpha-trinositol a unique cardiovascular profile.