Abstract
The effects of brimonidine, an α2-adrenoceptor agonist, on blood pressure, heart rate, respiratory rate, renal function and some blood parameters were investigated in 10 dogs. Dogs were divided into two groups, low dose (LD; 0.2 mg/kg) and high dose (HD; 0.5 mg/kg) of brimonidine given orally. The α2-adrenergic antagonist yohimbine hydrochloride was injected to dogs at a dose of 0.1 mg/kg in both groups at the fifth hour after brimonidine administration. The results demonstrated that after administration of brimonidine, mean arterial blood pressure decreased dramatically at 2 h by 23% and 20% in LD and HD groups, respectively. Heart rate was decreased in a similar manner and both remained low at 5 h after brimonidine administration. Respiratory rate was decreased by 50%, while the electrocardiogram showed prolongation of the PR interval. Glomerular filtration rate (GFR) and effective renal blood flow were reduced when measured at 4 h after brimonidine ingestion in both groups, but the effect was more pronounced in the LD group. Brimonidine caused natriuresis and kaliuresis in both LD and HD groups. The packed cell volume was decreased and hyperglycaemia was detected. Most of the effects can be reversed completely after administration of yohimbine. However, yohombine can restore GFR only partially. These data suggest that brimonidine caused cardiovascular and respiratory depression. The adverse effects of this drug can be antagonized by yohimbine, suggesting that these effects were mediated via the α2-adrenoceptor.
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Abbreviations
- \( C_{{\rm H_{2}O}} \) :
-
free water clearance
- C osm :
-
osmolar clearance
- ECG:
-
electrocardiography/electrocardiogram
- ERBF:
-
effective renal blood flow
- ERPF:
-
effective renal plasma flow
- FECa :
-
fractional excretion of Ca2+
- FECl :
-
fractional excretion of Cl−
- FEe :
-
electrolytes
- FEK :
-
fractional excretion of K+
- FENa :
-
fractional excretion of Na+
- FEPi :
-
fractional excretion of inorganic phosphate
- FF:
-
filtration fraction
- GFR:
-
glomerular filtration rate
- HD:
-
high dose
- LD:
-
low dose
- MAP:
-
mean arterial pressure
- NTS:
-
nucleus tractus solitarius
- PAH :
-
para-aminohippuric acid
- PCV:
-
packed cell volume
- RR:
-
respiratory rate
- RT:
-
rectal temperature
- RVLM:
-
rostral ventrolateral medial
- RVR:
-
renal vascular resistance
- TS:
-
total solids
- V :
-
urine flow rate
References
Arata, A., Onimaru, H. and Homma, I., 1998. The adrenergic modulation of firings of respiratory rhythm-generating neurons in medulla-spinal cord preparation from newborn rat. Experimental Brain Research, 119(4), 399–408
Bernstein, I.M., Shapiro, R.E., Whitsel, A. and Schonberg, A.L., 2003. Relationship of plasma volume to sympathetic tone in nulliparous women. American Journal of Obstetrics and Gynecology, 188(4), 938–942
Bock, C., Niederhoffer, N. and Szabo, B., 1999. Analysis of receptor involved in the central hypotensive effect of rilmenidine and moxinidine. Naunyn Schmiedeberg’s Archives of Pharmacology, 359, 262–271
Brun, C., 1951. A rapid method for the determination of para-aminohippuric acid in kidney function tests. Journal of Laboratory and Clinical Medicine, 37, 955–958
Buranakarl, C., Kijtawornrat, A. and Nampimoon, P., 2001. Effects of fosinopril on renal function, baroreflex response and noradrenaline pressor response in conscious normotensive dogs. Veterinary Research Communications, 25, 355–366
Burke, J., Kharlamb, A., Shan, T., Runde, E., Padillo, E., Manlapaz, C. and Wheeler, L., 1995. Adrenergic and imidazoline receptor-mediated responses to UK-14, 304–18 (brominidine) in rabbits and monkeys. A species difference. Annals of the New York Academy of Sciences, 10(3), 220–226
Carlsen, J.O., Zabriskie, N.A., Kwon, Y.H., Barbe, M.E. and Scott, W.E., 1999. Apparent central nervous system depression in infants after the use of topical brimonidine. American Journal of Ophthalmology, 128(2), 255–256
Cullen, L.K., 1996. Medetomidine sedation in dogs and cats: a review of its pharmacology, antagonism and dose. British Veterinary Journal, 152, 519–535
DeFronzo, R.A., Goldberg, M. and Agus, Z.S., 1976. The effects of glucose and insulin on renal electrolyte transport. Journal of Clinical Invesigation, 58, 83–90
Duggan, S., Hong, M., Milne, B. and Jhamandas, K., 1994. The role of excitatory amino acid in the expression of precipitated acute and chronic clonidine withdrawal: an in vivo voltammetric study in the rat locus coeruleus. Brain Research, 665, 253–261
Gabelt, B.T., Robinson, J.C., Hubbard, W.C., Peterson, C.M., Debink, N., Wadhwa, A. and Kaufman, P.L., 1994. Apraclonidine and brimonidine effects on anterior ocular and cardiovascular physiology in normal and sympathectomized monkeys. Experimental Eye Research, 59(6), 633–644 (abstract)
Garcia-Barrado, M.J., Sancho, C., Palomero, J. and Moratinos, J., 1998. Role of α2-adrenoceptors on the hyperglycemic and insulin secretory effects derived from α1- and β-adrenoceptor stimulation in the rabbit. Journal of Autonomic Pharmacology, 18(5), 287 (abstract)
Gomori, G.A., 1942. Modification of the colorimetric phosphorus determination for use with the photoelectric colorimeter. Journal of Laboratory and Clinical Medicine, 27, 955–960
Greenfield, D.S., Liebmann, J.M. and Ritch, R., 1997. Brimonidine: a new alpha 2-adrenoreceptor agonist for glaucoma. Journal of Glaucoma, 6(4), 250–258
Janssen, B.J.A., Lukoshkova, E.V. and Head, G.A., 2001. Sympathetic modulation of renal blood flow by rilmenidine and captopril: central vs. peripheral effects. American Journal of Physiology, 282, F113-F123
Kubo, T., Goshima, Y., Hata, H. and Misu, Y., 1990. Evidence that endogenous catecholamines are involved in α2 adrenoceptor-mediated modulation of the aortic baroreceptor reflex in the nucleus tractus solitarii of the rat. Brain Research, 526, 313–317
Kuusela, E., Raekallio, M., Vaisanen, M., Mykkanen, K., Ropponen, H. and Vainio, O., 2001. Comparison of medetomidine and dexmedetomidine as premedicants in dogs undergoing propofol–isoflurane anesthesia. American Journal of Veterinary Research, 62(7), 1073–1080
Moorehead, U.R. and Biggs, H.G., 1974. 2-Amino-2 methyl-1-propanol as the alkalinizing agent in an improved continuous -flow cresolphthalein complexone procedure for calcium in serum. Clinical Chemistry, 20, 1458–1460
Muir, W.W. and Piper, F.S., 1977. Effect of xylazine on indices of myocardial contractility in the dog. American Journal of Veterinary Research, 38(7), 931–934
Ojiri, Y., Noguchi, K., Chibana, T. and Sakanashi, M., 1993. Effects of adrenergic stimulants on the splenic diameter, haemoglobin content and haematocrit in anaesthetized dogs: determination of the adrenoceptor subtype responsible for changes in the splenic diameter. Acta Physiologica Scandinavica, 149(1), 31–39
Ota, K., Kimura, T., Shoji, M., Inoue, M., Sato, K., Ohta, M., Yamamoto, T., Tsunoda, K., Abe, K. and Yoshinaga, K., 1990. Effects of intracerebroventricular administration of adrenoceptor agonists on the regulation of renal water and electrolytes handling through endocrine, renal and hemodynamic function. Tohoku Journal of Experimental Medicine, 162(1), 27–39
Pypendop, B.H. and Verstegen, J.P., 2001. Cardiovascular effects of romifidine in dogs. American Journal of Veterinary Research, 62, 490–495
Smyth, D.D., Umemura, S. and Pettinger, W.A., 1985. Renal nerve stimulation causes alpha 1-adrenoceptor-mediated sodium retention but not alpha 2-adrenoceptor antagonism of vasopressin. Circulatory Research, 57(2), 304–311
Stranhoy, J.W., 1985. Role of alpha-2 receptors in the regulation of renal function. Journal of Cardiovascular Pharmacology, 7(Supplement 8), S28–S33
Sved, A.F., Tsukamoto, K. and Schreihofer, A.M., 1992. Stimulation of α2-adrenergic receptors in the nucleus tractus solitarius is required for the baroreceptor reflex. Brain Research, 576, 297–303
Sztajnbok, J., 2002. Failure of naloxone to reverse brimonidine-induced coma in an infant. Journal of Pediatrics, 140(4), 485–486
Takahashi, K., Hisa, H. and Satoh, S., 1984. Effects of alpha-agonist on renin and prostaglandin E2 release in anesthetized dogs. American Journal of Physiology, 247, E604–608
Tilley, L.P, 1992. The approach to the electrocardiogram. In: Essentials of Canine and Feline Electrocardiography, 3rd edn, (Lea and Febiger, Philadelphia), 50
Walters, T.R., 1996. Development and use of brimonidine in treatment of acute and chronic elevation of intraocular pressure: a review of safety, efficacy, dose response and dosing studies. Survey of Ophthalmology, 41 supplement 1, s19–26
Welch, S.L. and Richardson, J.A., 2002. Clinical effects of brimonidine ophthalmic drops ingestion in 52 dogs. Veterinary and Human Toxicology, 44(1), 34–35
Yamazaki, T. and Ninomiya, I., 1993. Noradrenaline contributes to modulation of the carotid sinus baroreflex in the tractus solitarii area in the rabbit. Acta Physiologica Scandinavica, 149, 1–6
Zornow, M.H., 1991. Ventilatory, hemodynamic and sedative effects of the alpha 2-adrenergic agonist, dexmedetomidine. Neuropharmacology, 30(10), 1065–1071
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Suwanwipat, S., Buranakarl, C. & Chaiyabutr, N. Effects of Brimonidine Ingestion on Cardiovascular Responses and Renal Function in Conscious Dogs. Vet Res Commun 31, 323–334 (2007). https://doi.org/10.1007/s11259-006-3414-1
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DOI: https://doi.org/10.1007/s11259-006-3414-1