Evaluation of Isolated Vascular Response to 5HT1A, 5HT1B1D & 5HT2A Receptors Agonist & Antagonist in Chronic Endotoxemic Rats

Abstract

The main vascular feature in endotoxemia is impaired contractile responses to vasoactive agents. We study the aortic response to 5HT[1]1 A, 5HT1B1D and 5HT2A receptors agonist and antagonist in chronic endotoxemic rats. Intraperitoneal injection of 1 mg/kg lipopolysaccharide for 5 days induced chronic endotoxemia. Control rats received intraperitoneal injection of 1 ml/kg saline for 5 days. Rats divided into 3 groups. In first, DOI[2] hydrochloride used as an agonist and sarpogrelate hydrochloride as an antagonist of 5HT2A receptor. In second, (R)-(+)-8-OH-DPAT[3] and WAY100135[4] used as an agonist and antagonist of 5HT1A receptor respectively. In third, Zolmitriptan used as an agonist and GR127935 hydrochloride as an antagonist of 5HT1B1D receptor. Aorta Isolated for organ bath study. Real time-PCR[5] and histopathological study examined receptors gene expression and protein localization. Cumulative 8-OH-DPAT caused relaxation in control aorta (EC50[6] 7.79±21.35 and 8.53±10.74 with and without antagonist), which was enhanced in endotoxemia (EC50 6.35±8.48 and very wide±17.38 with and without antagonist). Cumulative zolmitriptan caused relaxation in control aorta (EC50 very wide±8.65 and 8.38±8.44 with and without antagonist), which was enhanced in endotoxemia (EC50 very wide±9.53 and 8.37±13.49 with and without antagonist). DOI hydrochloride contracted the control aorta (EC50 6.51±7.14 and 5.98±1.65 with and without antagonist), which was converted to relaxation in endotoxemic group (EC50 infinity±80.43 and 7.37±20.28 with and without antagonist). PCR studies revealed enhanced 5HT1A receptor and diminished 5HT1B1D and 5HT2A receptor genes expression, while histopathological studies showed inflamed, damaged endothelium in endotoxemic aorta. Our data supports enhanced vasodilation and impaired vasoconstriction during endotoxemia.

Key words

endothelium - vasodilation - endotoxins - aorta - serotonin

¹ 5-hydroxytryptamine

² (±)-DOI, (±)-1-(2,5-Dimethoxy-4-iodophenyl)-2-aminopropane hydrochloride

³ (R)-(+)-2-Dipropylamino-8-hydroxy-1,2,3,4-tetrahydronaphthalene hydrobromide

⁴ 3-[4-(2-Methoxyphenyl)piperazin-1-yl]-2-phenyl-N-tert-butyl-propanamide dihydrochloride

⁵ Polymerase chain reaction

⁶ Half maximal effective concentration

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