Summary
Based on previous in vitro studies, we hypothesised that endothelin (ET) would induce vasoconstriction in the pulmonary circululation of the horse and that this action would be mediated via ETA receptors. Pulmonary and systemic haemodynamic responses to endothelin‐1 (ET‐1), a potent vasoactive endogenous peptide, were investigated in 6 conscious, nonsedated horses at rest. Bolus i.v. injections of exogenous ET‐1 (0.1, 0.2 and 0.4 μg/kg bwt) caused significant increases in pulmonary (PAP) and carotid (CAP) artery pressures, with peak increases of 79% and 51% for mean PAP and CAP, respectively. The effect of ET‐1 on PAP and CAP was rapid and transient for PAP (∼10 min) but prolonged for CAP (up to 60 min). ET‐1 significantly decreased cardiac output by up to 35% and significantly increased systemic vascular resistance (SVR) by up to 104%. Pulmonary vascular resistance (PVR) showed a trend (P>0.05) to increase with 0.2 and 0.4 μg/kg bwt ET‐1. Infusion of a selective ETA receptor antagonist (TBC11251) completely inhibited the responses to a subsequent bolus of 0.2 μg/kg bwt ET‐1. We conclude that exogenous ET‐1 exerts a potent vasoconstrictive action on the pulmonary and systemic circulations of the horse. These effects appear to be mediated largely through ETA receptors in both circulations. Endothelin may play a role in hypertensive conditions in the horse.
Summary
Reasons for performing study: There is currently little published information about the effects of endothelin‐1 (ET‐1), a potent endogenous spasmogen of vascular and airway smooth muscle, on pulmonary vasculature and airways or which ET receptor subtypes mediate ET‐1‐induced vasoconstrictive and bronchoconstrictive action in the horse.
Objectives: To investigate the effect of endothelin‐1 (ET‐1) on smooth muscle from isolated equine pulmonary artery and bronchus. In addition, the roles of ETA and ETB receptors in ET‐1 mediated contraction in these tissues were assessed.
Methods: The force generation of ring segments from pulmonary arteries or third‐generation airways (obtained from horses subjected to euthanasia fororthopaedic reasons) were studied in an organ bath at 37°C in response to exogenous endothelin and selective endothelin A (BQ123) or B receptor (BQ788) antagonists.
Results: ET‐1 produced concentration‐dependent contractions of the equine pulmonary artery and bronchus. The threshold for contraction was 10−10 and 10−9 mol/l ET‐1 for pulmonary artery and bronchus, respectively. The maximal contraction induced by the highest ET‐1 concentration (10−7 mol/l) was 173 and 194% of the contraction obtained with 100 mmol/l KCl in pulmonary artery and bronchus, respectively. ET‐1 potency was 25 times greater in equine pulmonary artery than in equine bronchus (concentration of ET‐1 producing 50% of maximal contraction [EC50] = 5.6 10−9 mol/l and 2.2 10−8 mol/l, respectively). In pulmonary artery, ET‐1 induced contractions were significantly inhibited by the ETA receptor antagonist BQ123 (1 μmol/l; dose‐response curve to ET‐1 was shifted to the right by 5.4‐fold), but not by the ETB antagonist BQ788. In bronchus, dose‐responses curves to ET‐1 were shifted to the right by BQ123 (1 μmol/l; 2.5‐fold), but not by BQ788 (1 μmol/l). In the presence of both antagonists, the dose‐response curve to ET‐1 was shifted to the right by 4.5‐fold.
Conclusions: These functional studies demonstrate that ET‐1 is a potent spasmogen of equine third generation pulmonary artery and bronchus, and that contractions are mediated via ETA receptors in the former and both ETA and ETB receptors in the latter.
Potential clinical relevance: Endothelin receptor antagonists may have potential for treating equine pulmonary hypertension or bronchoconstriction.
Summary
The changes in carnitine in plasma and milk during the first 3 months of lactation were studied in 14 broodmares and their foals. Six of the mares (Group S) were given a supplement of 10 g carnitine split between the morning and evening feeds, starting 2 weeks before birth.
At birth the plasma carnitine concentration in Group S mares was about twice that in Group NS mares (no supplement). In both groups the concentration initially declined in the days after birth. Whilst this trend was reversed in Group S mares, the concentration in Group NS mares remained at a reduced level for the remainder of the study. Milk concentrations declined continuously over the monitoring period in both groups. There was no apparent relationship between milk and plasma concentrations. Despite this the milk concentration tended to be higher in Group S than in Group NS mares although differences were not significant. There was an immediate drop in the plasma concentration in foals after birth which was reversed in foals of Group S mares but not in those of Group NS mares. There were no apparent side effects of carnitine supplementation.
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