Vasoconstrictor effect to 5HT, histamine and phenylephrine in pulmonary artery and its modulation by hypoxia
Author(s):
Santwana Palai and Subash Chandra Parija
Abstract:
Hypoxia in lung diseases like chronic obstructive pulmonary disease, pulmonary arterial hypertension, pulmonary oedema etc. exhibit vasoconstriction, remodelling of the pulmonary vessel wall and thrombosis which leads to increased pulmonary vascular resistance. The pulmonary artery of Capra hircus is taken as pulmonary vascular model to evaluate effects of several vasocontractile agents so as to understand the mechanisms involved as pharmacological basis for therapeutics in the treatment of pulmonary arterial hypertension. The secondary branch of pulmonary artery mounted in automatic organ bath was exposed to vasotonic agent like 5HT, Histamine and α-adrenergic agonist under normoxic and hypoxic conditions. Hypoxia reduced the affinity of 5HT by 1.06 log units and Emax by 63%. 5HT induced contractile response was reduced by 35.1% and 70% with decrease in affinity by 1.32 and increase in affinity by 0.36 log unit by Ondansetron in normoxic and hypoxic rings, respectively, when compared with respective control. Hypoxia reduced affinity of Histamine by 0.16 log units and Emax by 63.6%. The Histamine induced contractile response was reduced by 37.7% with decrease in affinity by 0.32 and 31.11% with decrease in affinity by 0.05 log unit by Ranitine in normoxic and hypoxic rings, respectively, when compared with respective control. Hypoxia increased affinity of PE by 0.1 log units and Emax by 80%. The PE induced contratile response was reduced by 77% and 88% with decrease in affinity by 0.52 and 0.73 log unit by Prazosin in normoxic and hypoxic rings, respectively as compared with respective control. The inhibition of serotonergic, histaminergic & α1-adrenergic receptor mediated vasototonic response is more in hypoxic than normoxic tissue suggesting hypoxia significantly reduced the sensitivity of serotonergic, histaminergic & α1-adrenergic receptor. The inhibition of serotonergic vasototonic response by Ondansetron ; histaminergic vasototonic response by Ranitine and α1-adrenergic receptor mediated vasototonic response by Prazosin more in hypoxic than normoxic tissue suggests that Ondansetron significantly augmented the vasorelaxation effect of 5HT; Ranitine significantly augmented the vasorelaxation effect of Histamine and Prazosin significantly augmented the vasorelaxation effect of α1-adrenergic receptor agonist contracted rings more in hypoxic than normoxic state.
How to cite this article:
Santwana Palai, Subash Chandra Parija. Vasoconstrictor effect to 5HT, histamine and phenylephrine in pulmonary artery and its modulation by hypoxia. Pharma Innovation 2017;6(9):225-230.