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Carroll, G. L., Matthews, N. S., Hartsfield, S. M., Slater, M. R., Champney, T. H., & Erickson, S. W. (1997). The effect of detomidine and its antagonism with tolazoline on stress-related hormones, metabolites, physiologic responses, and behavior in awake ponies. Vet Surg, 26(1), 69–77.
Abstract: Six ponies were used to investigate the effect of tolazoline antagonism of detomidine on physiological responses, behavior, epinephrine, norepinephrine, cortisol, glucose, and free fatty acids in awake ponies. Each pony had a catheter inserted into a jugular vein 1 hour before beginning the study. Awake ponies were administered detomidine (0.04 mg/kg intravenously [i.v.]) followed 20 minutes later by either tolazoline (4.0 mg/kg i.v.) or saline. Blood samples were drawn from the catheter 5 minutes before detomidine administration (baseline), 5 minutes after detomidine administration, 20 minutes before detomidine administration which was immediately before the administration of tolazoline or saline (time [T] = 0), and at 5, 30, and 60 minutes after injections of tolazoline or saline (T = 5, 30, and 60 minutes, respectively). Compared with heart rate at T = 0, tolazoline antagonism increased heart rate 45% at 5 minutes. There was no difference in heart rate between treatments at 30 minutes. Blood pressure remained stable after tolazoline, while it decreased over time after saline. Compared with concentrations at T = 0, tolazoline antagonism of detomidine in awake ponies resulted in a 55% increase in cortisol at 30 minutes and a 52% increase in glucose at 5 minutes. The change in free fatty acids was different for tolazoline and saline over time. Free fatty acids decreased after detomidine administration. Free fatty acids did not change after saline administration. After tolazoline administration, free fatty acids increased transiently. Tolazoline tended to decrease sedation and analgesia at 15 and 60 minutes postantagonism. Antagonism of detomidine-induced physiological and behavioral effects with tolazoline in awake ponies that were not experiencing pain appears to precipitate a stress response as measured by cortisol, glucose, and free fatty acids. If antagonism of an alpha-agonist is contemplated, the potential effect on hormones and metabolites should be considered.
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Nicol, C. J., Adachi, M., Akiyama, T. E., & Gonzalez, F. J. (2005). PPARgamma in endothelial cells influences high fat diet-induced hypertension. Am J Hypertens, 18(4 Pt 1), 549–556.
Abstract: BACKGROUND: Peroxisome proliferator-activated receptor gamma (PPARgamma) ligands improve human hypertension. However, the mechanism and site of this effect remains unknown, confounded by PPARgamma expression in many cell types, including endothelial cells (ECs). METHODS: To evaluate the vascular role of PPARgamma we used a conditional null mouse model. Specific disruption of PPARgamma in ECs was created by crossing Tie2-Cre+ transgenic (T2T+) and PPARgamma-floxed (fl/fl) mice to generate PPARgamma (fl/fl)T2T+ (PPARgamma E-null) mice. Conscious 8- to 12-week-old congenic PPARgamma (fl/fl)Cre- (wild type) and PPARgamma E-null mice were examined for changes in systolic blood pressure (BP) and heart rate (HR), untreated, after 2 months of salt-loading (drinking water), and after treatment for 3 months with high fat (HF) diet alone or supplemented during the last 2 weeks with rosiglitazone (3 mg/kg/d). RESULTS: Untreated PPARgamma E-nulls were phenotypically indistinguishable from wild-type littermates. However, compared to similarly treated wild types, HF-treated PPARgamma E-nulls had significantly elevated systolic BP not seen after normal diet or salt-loading. Despite sex-dependent baseline differences, salt-loaded and HF-treated PPARgamma E-nulls of either sex had significantly elevated HR versus wild types. Interestingly, rosiglitazone improved serum insulin levels, but not HF diet-induced hypertension, in PPARgamma E-null mice. CONCLUSIONS: These results suggest that PPARgamma in ECs not only is an important regulator of hypertension and HR under stressed conditions mimicking those arising in type 2 diabetics, but also mediates the antihypertensive effects of rosiglitazone. These data add evidence supporting a beneficial role for PPARgamma-specific ligands in the treatment of hypertension, and suggest therapeutic strategies targeting ECs may prove useful.
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Youket, R. J., Carnevale, J. M., Houpt, K. A., & Houpt, T. R. (1985). Humoral, hormonal and behavioral correlates of feeding in ponies: the effects of meal frequency. J. Anim Sci., 61(5), 1103–1110.
Abstract: The effect of meal frequency on body fluid, glucose, triiodothyronine (T3), heart rate and behavior was measured in 10 ponies. A simple reversal design was used in which each pony received one meal/day (1X) for 2 wk and six meals/day (6X) for 2 wk. The total intake/day was held constant. Feeding was followed by a rise in plasma levels of glucose, T3, protein and osmolality. One large meal was followed by significantly greater changes in all of the variables than was a meal one-sixth the size. Plasma T3 rose from 41 +/- 5 (SE) ng/liter before feeding to 43 +/- 5 ng/liter following a small meal, but rose significantly higher, from 39 +/- 4 to 60 +/- 10 ng/liter, following a large meal. Glucose rose from 84 +/- 3 to 109 +/- 7 mg/dl following a small meal and rose significantly higher, from 83 +/- 3 to 154 +/- 11 mg/dl, after a large meal. Plasma protein rose from 6.55 +/- .14 to 6.62 +/- .16 g/dl following a small meal and from 6.45 +/- .14 to 6.99 +/- .11 g/dl following a large meal. Osmolality rose from 227 +/- 1 mosmol/liter before to 279 +/- 1 mosmol/liter following a small meal and significantly higher from 278 +/- 2 to 285 +/- 1 mosnol/liter following a large meal. Heart rate rose from 42 beats/min in the absence of feed to 50 beats/min when food was visible to the ponies and did not rise higher when eating began. There were no significant differences in the cardiac response to one large meal and that to a small meal.(ABSTRACT TRUNCATED AT 250 WORDS)
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