Objective—To characterize the in vitro response of
circular and longitudinal myometrial layers of the uterine
horn (CMLH and LMLH, respectively) of horses to
endothelin (ET)-1 by use of specific ETA (BQ-123) and
ETB (IRL-1038) receptor antagonists.
Sample Population—Uteruses from 10 nongravid
mares in anestrus.
Procedure—Muscle strips from the CMLH and
LMLH were suspended in tissue baths and connected
to force-displacement transducers interfaced with
a polygraph. Strips were incubated for 45-minute
intervals with no antagonist (control specimens), and
3 concentrations (10–9, 10–7, and 10–5M) of BQ-123, IRL-
1038, or BQ-123 and IRL-1038 before concentrationresponse
curves to ET-1 were generated. Contractile
response to cumulative concentrations of ET-1 (10–9 to
10–6M) was quantified by measuring change in the
area under the curve (AUC) for the 3-minute period
after each ET-1 dose.
Results—ET-1 caused concentration-dependent contraction
of the CMLH and LMLH specimens.
Application of BQ-123 decreased AUC values for both
layers. Application of IRL-1038 increased the AUC value
for LMLH specimens but did not affect the CMLH
value. The combination of BQ-123 and IRL-1038
decreased the AUC value for LMLH tissue and
increased that for CMLH tissue.
Conclusions and Clinical Relevance—ET-1 causes contraction
of the CMLH and LMLH in nongravid horses. In
both layers, ETA receptors mediate contraction but the
role of ETB receptors remains unclear. In the LMLH, ETA
receptors have a dominant role; the presence of another
receptor or receptor subtype within this layer is suggested.
These findings support a physiologic role for ET-1 in
uterine contractility. (Am J Vet Res 2005;66:1094–1100)
Objective—To establish an in vivo method for matrix metalloproteinase (MMP)-2 and MMP-9 induction in horses via IV administration of lipopolysaccharide (LPS) and to evaluate the ability of doxycycline, oxytetracycline, flunixin meglumine, and pentoxifylline to inhibit equine MMP-2 and MMP-9 production.
Animals—29 adult horses of various ages and breeds and either sex.
Procedures—In part 1, horses received an IV administration of LPS (n = 5) or saline (0.9% NaCl) solution (5). Venous blood samples were collected before and at specified times for 24 hours after infusion. Plasma was harvested and analyzed for MMP-2 and MMP-9 activities via zymography. In part 2, horses received doxycycline (n = 5), oxytetracycline (5), flunixin meglumine (5), or pentoxifylline (4) before and for up to 12 hours after administration of LPS. Plasma was obtained and analyzed, and results were compared with results from the LPS-infused horses of part 1.
Results—Administration of LPS significantly increased MMP-2 and MMP-9 activities in the venous circulation of horses. All MMP inhibitors significantly decreased LPS-induced increases in MMP activities but to differing degrees. Pentoxifylline and oxytetracycline appeared to be the most effective MMP-2 and MMP-9 inhibitors, whereas doxycycline and flunixin meglumine were more effective at inhibiting MMP-2 activity than MMP-9 activity.
Conclusions and Clinical Relevance—IV administration of LPS to horses caused increased venous plasma activities of MMP-2 and MMP-9. These MMP activities were reduced by pentoxifylline and oxytetracycline, suggesting that further evaluation of these medications for treatment and prevention of MMP-associated diseases in horses is indicated.
Objective—To evaluate the in vitro effects of adenosine
tryphosphate (ATP) on vasomotor tone of equine
Sample Population—Arteries and veins from the left
ventral colon of 14 mixed-breed horses euthanatized
for reasons unrelated to cardiovascular or gastrointestinal
Procedures—Endothelium-intact and -denuded arterial
and venous rings were precontracted with 10–7 and
1.8 × 10–8M endothelin-1, respectively. In 1 trial,
endothelium-intact rings were also incubated with
10–4M Nω-nitro-L-arginine methyl ester (L-NAME) to
inhibit nitric oxide (NO) production. Adenosine
triphosphate (10–8 to 10–3M) was added in a noncumulative
manner, and relaxation percentage versus time
curves were generated. Areas under the curves (ie,
percentage of relaxation time) were calculated.
Results—Relaxation response of arterial and venous
rings to ATP was dose-dependent. Percentage of
relaxation time in response to 10–4 and 10–3M ATP was
significantly greater, compared with that for rings not
treated with ATP. Removal of endothelium attenuated
but did not eliminate the relaxation response. Addition
of L-NAME did not attenuate the relaxation response
in arteries. At higher concentrations, the vascular
response to ATP was biphasic.
Conclusions and Clinical Relevance—ATP applied to
equine colonic arterial and venous rings with and without
intact endothelium induced a biphasic response
characterized by transient contraction followed by slow,
substantial, and sustained relaxation. This ATP-induced
response is possibly mediated by a mechanism other
than NO. Adenosine triphosphate may be a useful
treatment to modulate colonic vasomotor tone in horses
with strangulating volvulus of the ascending colon.
(Am J Vet Res 2001;62:1928–1933)
Objective—To evaluate the effectiveness of 2 potential
endothelin (ET)-1 antagonists in blocking the contractile
responses of equine colonic vessels to
increasing concentrations of ET-1.
Sample Population—Mesenteric vessels from 6
clinically healthy horses.
Procedure—Colonic vessels (arterial and venous
rings) were placed in organ baths with oxygenated
Tyrode solution at 37 C. Each was attached to a force
transducer interfaced with a polygraph, and 2 g of
tension was applied and equilibrated for 45 minutes.
Then, B-1 (PD 142893) and B-2 (PD 145065) ET-1
antagonists were tested. One ring from each vessel
type was used as a control for determining concentration-
response relationships of ET-1 (10–10 to 10–6M).
Three rings of each vessel type were incubated with
3 concentrations of each antagonist (10–7, 10–6, and 10
–5M) for 30 minutes before ET induced contractions
were determined. The maximum contractile
response and pA2 values were determined.
Results—Vessels contracted in a concentrationdependent
manner to ET-1. Arteries responded slowly
but reached greater contractions. Veins responded
immediately with sustained contractions. Both antagonists
inhibited contractions in a concentrationdependent
manner with significant differences at 10–6
and 10–5M for arteries and 10–5M for veins. Complete
blockade of contractions was observed with B-2
(10–5M). The pA2 values for B-1 were 8.26 and 6.82 for
arteries and veins, respectively, whereas they were
8.25 and 7.21 for B-2.
Conclusion and Clinical Relevance—Both antagonists
effectively blocked ET-1-induced contractions of
equine colonic vessels. Because B-2 is water soluble
and caused complete blockade at 10–5M, it appears to
be the preferred antagonist. (Am J Vet Res 2001;62:154–159)
Objective—To compare responses of bronchial rings
obtained from healthy horses and horses affected
with summer pasture-associated obstructive pulmonary
disease (SPAOPD) to selected mediators of
airway hyperreactivity in vitro.
Sample Population—Bronchial rings from 6 healthy
horses and 6 horses affected with SPAOPD.
Procedure—Bronchial rings obtained from each
group of horses were mounted in organ baths and
attached to force transducers interfaced with a polygraph.
After applying 2g of tension, each ring was
allowed to equilibrate for 45 minutes in Tyrode's solution
at 37 C. Cumulative concentration-response relationships
to graded concentrations of selected mediators
(10–8 to 10–4 M ) were determined and analyzed
for significance at each concentration.
Results—Acetylcholine, histamine, 5-hydroxytryptamine,
and leukotriene D4 induced concentrationdependent
contractile responses in bronchial rings.
Prostaglandin F2α induced weak and inconsistent contractile
responses. The other 2 agents, norepinephrine
and substance P, did not induce concentrationdependent
responses. Considering the overall groupdrug
effect, acetylcholine, histamine, 5-hydroxytryptamine,
and leukotriene D4 were effective in inducing
consistent concentration-dependent contractile
responses in both groups. Only 5-hydroxytryptamine
and histamine induced significant responses
in contractility between groups. The response of
bronchial rings from horses with SPAOPD to 5-hydroxytryptamine
was significantly greater than those
from control horses, whereas the response to histamine
was significantly lower. Significant responses
were evident at concentrations ranging from 10–6 to
10–4M for both drugs.
Conclusions and Clinical Relevance—Because the
airways of horses with SPAOPD had increased
responsiveness to 5-hydroxytryptamine in vitro, treatment
modalities using 5-hydroxytryptamine antagonists
should be investigated to address this phenomenon.
(Am J Vet Res 2001;62:259–263).
Objective—To correlate clinical score, intrapleural
pressure, cytologic findings of bronchoalveolar lavage
fluid (BALF), and histologic lesions of pulmonary tissue
in horses affected with summer pasture-associated
obstructive pulmonary disease (SPAOPD).
Animals—8 adult horses affected with SPAOPD and
6 adult horses without evidence of respiratory tract
Procedure—Clinical score, change in intrapleural
pressure (ΔPpl) during tidal breathing, results of cytologic
examination and bacteriologic culture of BALF,
and results of histologic examination of pulmonary
parenchyma were evaluated.
Results—Clinical scores for SPAOPD-affected horses
(median, 5.75; range, 4.0 to 7.5) were significantly
greater, compared with clinically normal horses
(median, 2.0; range, 2.0 to 3.0). Cytologic examination
of BALF from SPAOPD-affected horses
revealed predominantly nondegenerate neutrophils.
Histologic lesions were identified throughout pulmonary
tissue and included severe accumulation of
mucus and neutrophils within the small airways,
metaplasia of bronchiolar goblet cells, and mild peribronchial
infiltrate. Histologic examination of specimens
collected via percutaneous biopsy was predictive
of disease and corresponded to findings at postmortem
examination. Clinical score and δPpl were
highly correlated with mucus accumulation in the
airways of affected horses. Peribronchial inflammatory
infiltrate correlated with percentage of neutrophils
in BALF of affected horses.
Conclusions and Clinical Relevance—Clinical scoring
and ΔPpl provided valid estimates of disease
severity. Findings from cytologic examination of
BALF of SPAOPD-affected horses varied, although,
in most instances, it was diagnostically useful.
Severe mucus accumulation in the airways was the
most remarkable histopathologic finding in SPAOPDaffected
horses. Examination of biopsy specimens
collected from pulmonary parenchyma was consistently
useful in diagnosing SPAOPD. (Am J Vet Res 2000;61:167–173)
Objective—To characterize alterations in systemic
and local colonic hemodynamic variables associated
with IV infusion of ATP-MgCl2 in healthy anesthetized
Animals—12 adult horses.
Procedure—Six horses were given ATP-MgCl2, IV,
beginning at a rate of 0.1 mg of ATP/kg of body
weight/min with incremental increases until a rate of
1.0 mg/kg/min was achieved. The remaining 6 horses
were given an equivalent volume of saline (0.9%
NaCl) solution over the same time period. Colonic and
systemic hemodynamic variables and colonic plasma
nitric oxide (NO) concentrations were determined
before, during, and after infusion.
Results—Infusion of ATP-MgCl2 caused a rate-dependent
decrease in systemic and colonic vascular resistance,
principally via its vasodilatory effects. A rate of
0.3 mg of ATP/kg/min caused a significant decrease in
systemic and colonic arterial pressure and colonic vascular
resistance without a significant corresponding
decrease in colonic arterial blood flow. Consistent alterations
in NO concentrations of plasma obtained from
colonic vasculature were not detected, despite profound
vasodilatation of the colonic arterial vasculature.
Conclusions and Clinical Relevance—Results
revealed that IV infusion of ATP-MgCl2 may be beneficial
in maintaining colonic perfusion in horses with
ischemia of the gastrointestinal tract, provided a sufficient
pressure gradient exists to maintain blood flow.
(Am J Vet Res 2001;62:1240–1249)
Objective—To determine concentrations of nitric
oxide (NO) in plasma and bronchoalveolar lavage fluid
(BALF) and localize nitric oxide synthesis in the lungs
of horses with summer pasture-associated obstructive
pulmonary disease (SPAOPD).
Animals—7 adult horses with SPAOPD and 6 clinically
normal adult horses.
Procedure—Severity of SPAOPD was determined by
use of clinical scores, change in intrapleural pressure
(ΔPpl) during tidal breathing, cytologic analysis of
BALF, and histologic evaluation of lung specimens
obtained during necropsy. Nitric oxide concentrations
in plasma, BALF, and epithelial lining fluid (ELF) were
determined by use of a chemiluminescent method.
Inducible nitric oxide synthase (iNOS) and nitrotyrosine
(NT) were localized in formalin-fixed lung specimens
by use of immunohistochemical staining, and
nicotinamide adenine dinucleotide phosphate
diaphorase (NADPHd) activity was localized in cryopreserved
specimens by use of histochemical staining.
Results—Plasma concentration of NO in affected
horses was slightly but not significantly greater than
concentration in nonaffected horses. Nitric oxide concentrations
in BALF or ELF did not differ between
groups. Immunoreactivity of iNOS in bronchial epithelial
cells of 3 of 5 lung lobes was greater in horses
with SPAOPD, compared with nonaffected horses.
However, staining for NT and NADPHd activity did not
differ between groups.
Conclusions and Clinical Relevance—Expression of
iNOS was greater in bronchial epithelial cells of horses
with SPAOPD, compared with nonaffected horses,
suggesting that NO may play a role in amplifying the
inflammatory process in the airways of horses with
this disease. (Am J Vet Res 2001;62:1381–1386)
Advancing equality and equity in society is creating positive change, and the time has come to critically evaluate veterinary medicine, which, by all metrics, lacks diversity. To keep pace with increasingly diverse demographics and recent surges in pet ownership among all racial/ethnic groups, significant efforts to enhance diversity, equity, inclusion, and belonging (DEIB) must occur in veterinary colleges and the profession. Recruiting more underrepresented students, building pipelines for diverse faculty/staff, and creating inclusive, welcoming environments where all can thrive are critical steps toward enhancing DEIB within our organizations and profession. Our goal is to share experiences and lessons learned from our intentional commitment to strengthen DEIB, with the hope that our journey will be helpful to others. Increasing diversity in the veterinary profession will be facilitated through removing barriers, creating inclusive work environments where all people feel they belong, and ensuring fair and equitable hiring and personnel management practices. These steps should in turn improve access and quality of veterinary care, ensure we are more representative of the communities we serve, increase revenue, and preserve the human-animal bond.
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