Role of the α-adrenergic system in femoral vascular reactivity in neonatal llamas and sheep: a comparative study between highland and lowland species

Abstract

Using an integrative approach at the whole animal, isolated vessels, and molecular levels, we tested the hypothesis that the llama, a species that undergoes pregnancy under the influence of the chronic hypoxia of high altitude, delivers offspring with an increased α-adrenergic peripheral vascular reactivity compared with neonates from lowland species. We studied the femoral vascular response to acute hypoxia in vivo, the reactivity of femoral vessels ex vivo, and the expression of femoral α1-adrenergic receptor subtypes using RT-PCR in vitro. The increase in femoral resistance during hypoxia was 3.6 times greater in newborn llamas than newborn sheep (P < 0.05). The sensitivity of the contractile response to noradrenaline (pD2 = 5.18 ± 0.06 vs. 4.84 ± 0.05, P < 0.05) and the maximal response (Rmax = 101.3 ± 1.4 vs. 52.4 ± 1.4% K+max, P < 0.05) and sensitivity (pD2 = 5.47 ± 0.03 vs. 4.57 ± 0.05, P < 0.05) to phenylephrine were higher in femoral vessels from newborn llamas than newborn sheep. Competitive inhibition with prazosin of noradrenaline-induced contraction followed by Schild analysis showed higher affinity in the llama than the sheep (pA2 = 10.08 ± 0.093 vs. 8.98 ± 0.263, respectively, P < 0.05), consistent with greater α1B-adrenergic receptor transcript expression observed in small femoral arteries from neonatal llama. The llama newborn demonstrates significantly greater α-adrenergic peripheral vascular reactivity compared with neonates from lowland species that could be partially explained by preferential expression of α1B-adrenergic receptor subtype.