Effects of IV and aerosol administration of 5-hydroxytryptamine (5-HT) on ventilation, pulmonary mechanics values, pulmonary arterial pressure, and heart rate were investigated in healthy unsedated Friesian calves. Minute volume increased significantly, mainly because of an increase in respiratory rate. Except for total pulmonary resistance after bolus injection, continuous administration of 5-HT given by either route caused significant alterations of lung dynamic compliance and total pulmonary resistance, the former decreasing to one-fifth of its baseline value and the latter increasing twofold. Pulmonary arterial pressure increased significantly, whatever the speed or route of administration. Administration of a bolus did not affect heart rate, whereas continuous iv administration of 5-HT as well by perfusion or by aerosol resulted in sustained tachycardia. It was concluded that 5-HT induces reversible bronchoconstriction and pulmonary vasoconstriction in healthy unsedated calves, 5-HT-induced functional alterations depend on the speed of administration, and excess of 5-HT production or depression in uptake by the lungs during bovine respiratory tract diseases could contribute to pulmonary dysfunction.

peer reviewed

peer reviewed | OBJECTIVE: To characterize the cardiovascular response to i.v. administration of serotonin (5-hydroxytryptamine [5-HT]) in calves. ANIMALS: 5 healthy unsedated Friesian calves. PROCEDURE: 41 5-HT administrations were performed: II slow infusions (duration, 5 minutes) and 30 bolus infusions (duration, 5 seconds). Cardiovascular function values were recorded before, during, and after the infusion. RESULTS: Slow infusion of 5HT first resulted in a brief period of severe bradycardia, then in sustained tachycardia with a concomitant increase in cardiac output. Systemic initial hypotension concomitant with bradycardia, then a pressor phase associated with an increase in systemic vascular resistance, and finally, a long-lasting hypotensive phase associated with decreased systemic vascular resistance. Pulmonary hypertension was associated with increased pulmonary vascular resistance, reflecting intense pulmonary vasoconstriction. Bolus infusion at increasing dosages resulted in dose-dependent bradycardia and systemic hypotension, followed by dose-dependent systemic hypertension. Unlike with slow infusion, neither the second tachycardiac nor the third systemic hypotensive phases were evident. CONCLUSIONS: 5-HT induces dose-dependent cardiovascular responses, including a reflex response followed by pulmonary and systemic vasoconstriction, in healthy calves. CLINICAL RELEVANCE: Determining the type of serotonergic receptors responsible for these responses may help to determine whether 5-HT is involved in the mechanisms underlying brisket disease in cattle.

peer reviewed | Effects of IV and aerosol administration of 5-hydroxytryptamine (5-HT) on ventilation, pulmonary mechanics values, pulmonary arterial pressure, and heart rate were investigated in healthy unsedated Friesian calves. Minute volume increased significantly, mainly because of an increase in respiratory rate. Except for total pulmonary resistance after bolus injection, continuous administration of 5-HT given by either route caused significant alterations of lung dynamic compliance and total pulmonary resistance, the former decreasing to one-fifth of its baseline value and the latter increasing twofold. Pulmonary arterial pressure increased significantly, whatever the speed or route of administration. Administration of a bolus did not affect heart rate, whereas continuous IV administration of 5-HT as well by perfusion or by aerosol resulted in sustained tachycardia. It was concluded that 5-HT induces reversible bronchoconstriction and pulmonary vasoconstriction in healthy unsedated calves, 5-HT-induced functional alterations depend on the speed of administration, and excess of 5-HT production or depression in uptake by the lungs during bovine respiratory tract diseases could contribute to pulmonary dysfunction.

Endotoxin given in vivo has been shown to inhibit endothelial dependent relaxation, and augment adrenergic (norepinephrine) contractions in isolated palmar digital arteries of horses. A study, using tumor necrosis factor (TNF) in vitro, was performed to determine the possible cause of these vascular alterations. Palmar digital arteries were surgically removed from 6 horses under general anesthesia, cut into 4-mm vascular rings (4 segments/horse), suspended in tissue baths, and attached to force displacement transducers for measurement of vascular tension. Four in vitro treatment groups were evaluated: group 1, control; group 2, TNF (5,100 pg of TNF/ml); group 3, 10x TNF (10 times previous TNF concentration); group 4, TNF plus L-arginine (5,100 pg of TNF/ml and 10(-6) M L-arginine). The appropriate drug(s) was/were added to each tissue bath 10 minutes before dose-response tests were performed for acetylcholine, bradykinin, norepinephrine, and 5-hydroxytryptamine (serotonin). Concentrations needed to induce 50% maximal relaxation or contraction (EC50) and maximal percentage relaxation or contraction were determined. Arteries exposed to TNF (group 2) had significantly (P = 0.04) decreased maximal relaxation to acetylcholine and increased maximal contraction to norepinephrine, compared with control arteries, but values did not differ from those for arteries of groups 3 and 4. Maximal relaxation to bradykinin or contraction to serotonin were not different between treatment groups. Mean EC50 values for bradykinin, norepinephrine, and serotonin did not differ among the 4 treatment groups. Mean EC50 values for arterial segments' response to acetylcholine in group 4 were significantly (P = 0.04) increased, compared with control segments, but did not differ from those for segments of groups 2 and 3. The decreased endothelial dependent relaxation to acetylcholine and enhanced maximal contraction to norepinephrine were similar to vascular alterations caused by endotoxin, indicating that TNF may be responsible for endotoxin-induced vascular changes in vitro and in vivo in horses.

A subpopulation of purified, interepithelial lymphocytes from porcine small intestinal mucosa contained cytoplasmic granules. Toluidine blue staining revealed metachromatic granules in 13.64% (606/4,450) cells. The cells had scant organelles, a single large nucleus with obvious invagination of the nuclear membrane, and prominent chromatin. Each cell contained 1 to 10 cytoplasmic membrane-bound granules, 0.6 to 1.5 microns in diameter. These findings indicated that the granular mucosal lymphocytes are related morphologically to mucosal mast cells. The presence of serotonin in the granules, confirmed by the serotonin releasing test, provided functional evidence that granular mucosal lymphocytes are related to mucosal mast cells.

The concentrations of dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), and 5-hydroxyindole-3-acetic acid (5-HIAA) in CSF obtained from the cisterna magna of 21 nonneurologically compromised dogs were determined by high-pressure liquid chromatography and electrochemical detection. A rapid method of sample preparation, which involved single filtration through a deproteinizing membrane, was used. Canine CSF obtained in this manner contained 5.78 +/- 0.78 ng of DOPAC/ml, 72.19 +/- 4.09 ng of HVA/ml, and 29.95 +/- 1.67 ng of 5-HIAA/ml. Linear regression analysis between HVA and 5-HIAA yielded a correlation coefficient of 0.4804. The neurotransmitter index, HVA/5-HIAA, was found to be more indicative of the dopaminergic metabolite HVA than the acid metabolite of serotonin, 5-HIAA (correlation coefficient with HVA = 0.5529 vs a correlation coefficient with 5-HIAA = -0.4462). A poor relationship (correlation coefficient = -0.1715) was found to exist between the 2 dopaminergic metabolites DOPAC and HVA in the CSF.

OBJECTIVE To investigate serum and plasma serotonin concentrations, percentage of serotonin-positive platelets, level of surface-bound platelet serotonin expression (mean fluorescence intensity [MFI]), and platelet activation (CD62 expression) in platelet-rich plasma from Cavalier King Charles Spaniels with myxomatous mitral valve disease (MMVD). ANIMALS Healthy dogs (n = 15) and dogs with mild MMVD (18), moderate-severe MMVD (19), or severe MMVD with congestive heart failure (CHF; 10). PROCEDURES Blood samples were collected from each dog. Serum and plasma serotonin concentrations were measured with an ELISA, and surface-bound platelet serotonin expression and platelet activation were determined by flow cytometry. RESULTS Dogs with mild MMVD had higher median serum (746 ng/mL) and plasma (33.3 ng/mL) serotonin concentrations, compared with MMVD-affected dogs with CHF (388 ng/mL and 9.9 ng/mL, respectively), but no other group differences were found. Among disease groups, no differences in surface-bound serotonin expression or platelet activation were found. Thrombocytopenic dogs had lower serum serotonin concentration (482 ng/mL) than nonthrombocytopenic dogs (731 ng/mL). In 26 dogs, a flow cytometry scatterplot subpopulation (FSSP) of platelets was identified; dogs with an FSSP had a higher percentage of serotonin-positive platelets (11.0%), higher level of surface-bound serotonin expression (MFI, 32,068), and higher platelet activation (MFI, 2,363) than did dogs without an FSSP (5.7%, 1,230, and 1,165, respectively). An FSSP was present in 93.8% of thrombocytopenic dogs and in 29.5% of nonthrombocytopenic dogs. CONCLUSIONS AND CLINICAL RELEVANCE A substantive influence of circulating serotonin on MMVD stages prior to CHF development in Cavalier King Charles Spaniels was not supported by the study findings. An FSSP of highly activated platelets with pronounced serotonin binding was strongly associated with thrombocytopenia but not MMVD.

Objective: To determine the isometric responses of isolated intrapulmonary bronchioles from cats with and without adult heartworm infection. Animals: 13 purpose-bred adult cats. Procedures: Cats were infected with 100 third-stage larvae or received a sham inoculation, and the left caudal lung lobe was collected 278 to 299 days after infection. Isometric responses of intrapulmonary bronchiolar rings were studied by use of a wire myograph. Three cycles of contractions induced by administration of 10μM acetylcholine were followed by administration of the contractile agonists acetylcholine, histamine, and 5-hydroxy-tryptamine. To evaluate relaxation, intrapulmonary bronchiolar rings were constricted by administration of 10μM 5-hydroxytryptamine, and concentration-response curves were generated from administration of sodium nitroprusside, isoproterenol, and substance P. Results: Compared with tissues from control cats, contractile responses to acetylcholine and 5-hydroxytryptamine were reduced in tissues from heartworm-infected cats. Relaxation to isoproterenol was significantly reduced in tissues from heartworm-infected cats. Relaxation to substance P was increased in tissues from heartworm-infected cats, but relaxation to sodium nitroprusside was unchanged. Conclusions and Clinical Relevance: Results suggested that despite increased bronchiolar wall thickness in heartworm-infected cats, a hyperreactive response of the bronchiolar smooth muscle is not the primary mechanism of respiratory tract clinical signs. Reduced response of the airway to isoproterenol may indicate refractoriness to bronchiolar relaxation in heartworm-infected cats.