Objective—To compare the responses of equine digital
arteries (EDAs) and equine digital veins (EDVs) to
endothelin-1 (ET-1) and determine the role of the
endothelium and type of receptors involved in the
modulation and mediation of those responses,
Sample Population—5 to 9 palmar digital
vessels/experiment from 28 healthy horses.
Procedure—Rings of dissected vessels were mounted
under tension between force transducer wires in
organ baths containing Krebs-Henseleit solution at
30oC. Responses of EDAs and EDVs (with intact [+e]
or denuded [–e] endothelium) to cumulative concentrations
of ET-1 (10–10 to 3 × 10–7 M) were compared.
For (+e)EDAs and (+e)EDVs precontracted with a
thromboxane-mimetic (U44069; 10–8 M) and (–e)EDAs
and (–e)EDVs, responses to an ETB receptor agonist
(S6c; 10–10 to 3 × 10–7 M) were evaluated. Responses to
ET-1 (10–7 M) in (–e)EDAs and (–e)EDVs were evaluated
after incubation with an ETA receptor antagonist (BQ-
123; 3 × 10–7 M), an ETB receptor antagonist (BQ-788;
3 × 10–7 M), or vehicle solution.
Results—Endothelin-1 induced a concentrationdependent
contraction of endothelium-intact and
-denuded EDAs and EDVs; EDVs were more sensitive.
Neither vessel type relaxed in response to S6c,
although 2 of the (–e)EDAs contracted mildly.
Whereas BQ-123 inhibited the (–e)EDA and (–e)EDV
responses to ET-1, BQ-788 had no effect.
Conclusions and Clinical Relevance—Endothelin-1
induced digital vasoconstriction (marked constriction
in veins). This action was unaffected by endothelium
and mediated predominantly by ETA receptors. These
findings suggest ET-1 can induce selective digital
venoconstriction. (Am J Vet Res 2003;64:1438–1443
Objective—To compare responses of equine digital arteries (EDAs) and veins (EDVs) to human-acalcitonin gene-related peptide (hαCGRP), evaluate effect of the endothelium, and characterize receptors and sources of endogenous CGRP.
Sample—Palmar digital vessels (5 to 9/experiment) from healthy adult horses killed at an abattoir.
Procedures—Vessel rings were mounted under tension in organ baths containing Krebs-Henseleit solution at 30°C, with relaxation responses examined in vessels preconstricted with a thromboxane-mimetic (3 × 10−8M). Responses of endothelium-intact (+e) and -denuded (−e) EDAs and EDVs to hαCGRP C10−10 to 3 × 10−7M) were compared. Following incubation with an hαCGRP receptor antagonist (hαCGRP8–37; 1μM), responses of EDA(−e) and EDV(−e) to hαCGRP (10−7M) were obtained. Responses of endothelium-intact and -denuded arteries and veins to hαCGRP (3 × 10−7M) or capsaicin (10−5M) were evaluated as well as responses of endothelium-intact and -denuded EDA and EDV to hαCGRP (10−10 to 10−6M) after incubation with endothelin-1 (ET-1; 10−12M).
Results—hαCGRP resulted in nonendothelium, concentration-dependent relaxation in EDAs and EDVs, with greater responses in EDAs. Treatment with hαCGRP8–37 had minimal effect on responses to hαCGRP in either vessel type. Capsaicin induced relaxation in both vessel types. There were no differences between responses to hαCGRP for vessels pretreated with ET-1 or vehicle.
Conclusions and Clinical Relevance—Both hαCGRP and capsaicin induced digital vasodilation unaffected by a functional endothelium. This suggested that endogenous CGRP likely emanates from sensory-motor nerves and may contribute to digital vasodilation.
Objective—To measure concentrations of amines
formed in the cecum of clinically normal ponies,
determine amine concentrations in plasma samples
collected in spring and winter, and compare concentrations
of amines and serotonin in plasma samples
obtained from clinically normal ponies and ponies predisposed
Sample Population—Cecal contents obtained from
10 ponies euthanatized at an abattoir and blood samples
obtained from 42 adult ponies.
Procedure—Cecal contents were assayed for amines
by high-performance liquid chromatography (HPLC).
Blood samples were collected at various times of the
year from 20 ponies predisposed to acute laminitis
and 22 clinically normal ponies. Plasma serotonin concentration
was measured by HPLC, and tryptamine
(TRP), tyramine (TYR), phenylethylamine (PEA), and
isoamylamine (IAA) were measured by liquid chromatography-
Results—15 amines were identified in cecal contents.
Plasma TRP, TYR, PEA, and IAA concentrations
ranged from 10pM to 100nM in both groups of
ponies. Plasma concentrations of serotonin or other
amines did not differ between clinically normal ponies
and those predisposed to laminitis; however, significantly
higher concentrations of TRP, PEA, and IAA
were found in samples obtained in the spring, compared
with winter samples.
Conclusions and Clinical Relevance—Various
amines are found in the cecum of ponies, several of
which can be detected in the plasma. Concentrations
increase significantly in the spring and may reach
concentrations close to the threshold for causing
vasoconstriction. Release of amines from the cecum
into the systemic circulation may contribute to hemodynamic
disturbances in horses and ponies with
acute laminitis. (Am J Vet Res 2003;64:1132–1138)
Objective—To measure plasma endothelin-1 (ET-1)
concentrations and digital blood flow in clinically
Animals—To measure plasma endothelin-1 (ET-1)
concentrations and digital blood flow in clinically
Procedure—On days 2 and 5 following surgery,
Doppler ultrasonographic digital arterial blood flow
measurements were obtained. Hematologic and biochemical
analyses were performed, and plasma concentrations
of ET-1 and endotoxin (lipopolysaccharide)
were determined. A scoring system based on 9 clinical
variables was used to assign horses to group B
(quartile with greatest cumulative score) or group A
(remaining 3 quartiles). Follow-up at 2.5 years was
obtained by telephone questionnaire.
Results—For all horses on day 2, median (interquartile
values) plasma ET-1 concentrations were 1.4 (0.8,
1.7) pg/mL, whereas on day 5, plasma ET-1 concentrations
were 1.0 (0.5, 1.6) pg/mL. On day 2, digital
blood flow was 0.057 (0.02, 0.07) mL/min in group A
horses and 0.035 (0.02, 0.03) mL/min in group B horses.
On day 5, plasma ET-1 concentration was significantly
(73%) higher in group B horses, compared with
group A horses. Thirty of 36 horses were alive at 2.5
years; group A horses were more likely to have survived
(odds ratio, 25; 95% confidence interval, 2.4 to
262). Significant associations were found between an
increase in digital pulses, hoof wall temperatures, or
both and increased digital blood flow (0.14 vs
0.04 mL/min) on day 2 and increased digital arterial
diameter (0.32 vs 0.23 cm) on day 5.
Conclusions and Clinical Relevance—Horses with
more severe endotoxemia had decreased digital
blood flow, increased plasma ET-1 concentrations,
and decreased long-term survival. (Am J Vet Res 2005;66:630–636)