Acidosis reduces the function and expression of α_1D-adrenoceptor in superior mesenteric artery of Capra hircus

Abstract

Objective:The objective of this study was to characterize the α1-adrenoceptor (α1-AR) subtypes and evaluate the effect of acidosis on α1-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 pHo 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 pHo 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 α1D-AR was compared at physiological and acidic pHo using reverse transcription-polymerase chain reaction (RT-PCR).Results:NA- and PE-induced contractile responses were attenuated proportionately with a decrease in extracellular pH (pHo), 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 pHo. Prazosin (1 nM, 10 nM, and 0.1 μM) inhibited the NA- and PE-induced contractile response at pHo 7.4 and the blocking effect of prazosin was potentiated at pHo of 6.0 and 5.0. RT-PCR analysis for α1D-AR in GSMA showed that the mRNA expression of α1D-AR was decreased under acidic pHo as compared to physiological pHo.Conclusion:(i) Adrenergic receptor mediates vasoconstriction in GSMA under normal physiological pHo, and α1D is the possible subtype involved in this event (ii) acidosis attenuates the vasocontractile response due to reduced function and expression of α1D-AR and also increased the release of endothelial-relaxing factors.

Acidosis potentiates endothelium-dependent vasorelaxation and gap junction communication in the superior mesenteric artery

“…The SMA was selected as an ex vivo acidosis model for study of vasomotor changes in small ruminants at molecular and functional levels. Previous studies from our laboratory have reported an attenuated vasocontractile response under acidosis (Mohanty et al, 2016). Therefore, it was considered important to examine the effect of acidosis on mediators of vasorelaxation in the SMA.…”

“…The arterial rings of 1.5–2 mm were then mounted between two fine stainless steel L-shaped hooks and kept under a resting tension of 1.5 g in a thermostatically controlled (37.0±0.5°C) 20 ml organ bath containing MKHS continuously aerated with Carbogen. Isometric contraction studies were performed as described previously with minor modifications (Anderson et al, 2014; Dash and Parija, 2013; Mohanty et al, 2016; Singh et al, 2016; Sharma et al, 2017). Briefly, the arterial rings were equilibrated for 90 min before recording of muscle tension, washed every 15 min (using MKHS freshly adjusted to pH 7.4 or 6.8) and the experiment repeated for both endothelium intact (ED+) and denuded (ED-) vessels wherever necessary.…”

“…Sub-maximal concentration of NA (10 μM) or KCl (60 mM), inferred from their concentration response curve (CRC) was used to obtain an initial phasic followed by a sustained contractile response (Mohanty et al, 2016). Acetyl choline- or sodium nitroprusside - (1 nM - 100 μM) induced vasorelaxation was elicited by its subsequent addition into organ bath at an interval of 4 min with a dose increment of 1 log unit in a cumulative manner for either ED+ or ED− SMA rings.…”

“…Present studies were performed in the SMA to determine the pathophysiological mechanisms and therapeutic targeting for ruminal acidosis leading to rumenitis, liver abscesses and laminitis (Penner et al, 2007). The mesenteric arteries are characterized with high sensitivity to extracellular pH (pH o ), high permeability to H + , a rapid (< 2 min) and sustained decrease in pH, and reproducibility of the preparation of isolated arterial rings for the functional and molecular studies (Celotto et al, 2008; Mohanty et al, 2016). The SMA was selected as an ex vivo acidosis model for study of vasomotor changes in small ruminants at molecular and functional levels.…”

Fetoplacental vascular effects of maternal adrenergic antihypertensive and cardioprotective medications in pregnancy

“…As we summarized in Aim 1, previous studies consistently show evidence of adrenergic receptor expression within the fetoplacental vasculature (Fig. 3), suggesting that agonist-activated adrenergic receptor pathways may alter vascular tone in the fetoplacental circulation [40,44,48,49,52,55–83].…”