Effects of chronic infusions of α-trinositol on regional and cardiac haemodynamics in conscious rats

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Abstract
1 Male, Long Evans rats (350–450 g) were chronically instrumented for the measurement of renal, mesenteric and hindquarters haemodynamics, and were given three consecutive, 24 h infusions of vehicle (sterile saline at 0.3 ml h−1; n = 8) or α-trinositol (d-mjyo-inositol-1,2,6-triphosphate) at 5, 20 and 80 mg kg−1 h−1 (0.3 ml h−1; n = 9). During infusion of α-trinositol at 5 or 20 mg kg−1 h−1, cardiovascular changes were little different from those seen during saline infusion. However, during infusion of α-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 from the changes seen in the saline group. Infusion of α-trinositol at the high dose in naive rats (n = 8) had even more marked vasodilator effects. 2 Two groups of rats (n = 8 in each), chronically instrumented for the measurement of cardiac haemodynamics, were given 48 h infusions of saline (0.3 ml h−1) or α-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, peak aortic flow, dF/dtmax and central venous pressure. In the animals receiving α-trinositol, with the exception of central venous pressure, all the above variables, together with total peripheral conductance, increased. 3 These results, collectively, indicate that incremental infusions of α-trinositol do not reveal its full vasodilator potential, possibly due to concurrent activation of counter-regulatory vasoconstrictor mechanisms. However, infusion of α-trinositol at a high dose causes substantial increases in renal, mesenteric and hindquarters flows and vascular conductances, supported by significant increases in indices of cardiac inotropism. Such effects, in the absence of significant hypotension, tachycardia or signs of desensitization, give α-trinositol a unique cardiovascular profile.

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