Acidosis reduces the function and expression of α-adrenoceptor in superior mesenteric artery of .

OBJECTIVE

The objective of this study was to characterize the α-adrenoceptor (α-AR) subtypes and evaluate the effect of acidosis on α-AR function and expression in goat superior mesenteric artery (GSMA).

MATERIALS AND METHODS

GSMA rings were mounted in a thermostatically controlled (37.0°C ± 0.5°C) organ bath containing 20 ml of modified Krebs-Henseleit solution, maintained at pH of 7.4, 6.8, 6.0, 5.5, 5.0, and 4.5. Noradrenaline (NA)- and phenylephrine (PE)-induced contractile response was elicited in the absence or presence of endothelium and prazosin at pH of 7.4, 6.0, and 5.0. The responses were recorded isometrically by an automatic organ bath connected to PowerLab and analyzed using Labchart 7.1.3 software. Expression of α-AR was compared at physiological and acidic pH using reverse transcription-polymerase chain reaction (RT-PCR).

RESULTS

NA- and PE-induced contractile responses were attenuated proportionately with a decrease in extracellular pH (pH), i.e. 7.4 → 6.8 → 6.0 → 5.5 → 5.0 → 4.5. Endothelium denudation increased the contractile response at both normal and acidic pH. Prazosin (1 nM, 10 nM, and 0.1 μM) inhibited the NA- and PE-induced contractile response at pH 7.4 and the blocking effect of prazosin was potentiated at pH of 6.0 and 5.0. RT-PCR analysis for α-AR in GSMA showed that the mRNA expression of α-AR was decreased under acidic pH as compared to physiological pH.

CONCLUSION

(i) Adrenergic receptor mediates vasoconstriction in GSMA under normal physiological pH, and α is the possible subtype involved in this event (ii) acidosis attenuates the vasocontractile response due to reduced function and expression of α-AR and also increased the release of endothelial-relaxing factors.