The effect of medetomidine, an α₂‐adrenoceptor agonist, on plasma atrial natriuretic peptide levels, haemodynamics and renal excretory function in spontaneously hypertensive and Wistar‐Kyoto rats

Abstract

1 The effects of the selective a2-adrenoceptor agonist, medetomidine, were assessed on plasma levels of immunoreactive atrial natriuretic peptide (IR-ANP), haemodynamics and on urine water and solute excretion in conscious, chronically cannulated, 7 month-old spontaneously hypertensive (SHR) and age-matched Wistar-Kyoto (WKY) rats, in order to examine the role of a2-adrenoceptors in the control of ANP secretion.2 A 60min i.v. infusion of medetomidine (0.2 or 0.6.ugkg-1min-') decreased heart rate dosedependently in both strains. Medetomidine infusion (0.6pgkg-1min-1) resulted in an increase in mean arterial pressure in WKY, whereas both doses decreased blood pressure in SHR. There was a slight increase in the right atrial pressure in both strains (WKY: + 1.18 + 0.26 mmHg; SHR: +1.64 + 0.64 mmHg, NS) in response to infusion of 0.6 pg kg-min-of medetomidine. 3 No differences were found in resting plasma IR-ANP levels between WKY (114 + 8 pg ml-, n = 19) and SHR (117 ± 10pgmlP, n = 21). Infusion of equibradycardic doses of medetomidine increased dose-dependently plasma IR-ANP levels in WKY, but did not affect the plasma IR-ANP concentration in SHR rats. 4 Despite the different effect of medetomidine on ANP release in WKY and SHR rats, i.v. administration of medetomidine affected renal excretory functions similarly in both strains; urine flow and sodium excretion increased and urine osmolality decreased significantly, while there was no consistent change in urinary potassium excretion. Urine osmolality decreased to hypo-osmotic levels during the infusion of 0.6 yg kg-1 min1 of medetomidine, suggesting a possible interaction between a2-adrenoceptor stimulation and the vasopressin system. 5 These results show that the a2-adrenoceptor agonist medetomidine increased plasma levels of ANP in WKY rats, probably through an increase in mean arterial and right atrial pressures, whereas the SHR had attenuated ANP release to a2-adrenoceptor stimulation. Our findings, that medetomidine caused marked natriuretic and diuretic effects in both strains and that these effects on the excretory functions of the kidneys were not related to changes in plasma levels of IR-ANP, demonstrate that changes in plasma ANP levels alone do not account for the diuretic and natriuretic effect of x2-agonists.

Comparison of the anesthetic effect by the injection route of mixed anesthesia (medetomidine, midazolam and butorphanol) and the effect of this anesthetic agent on the respiratory function

“…Blood Na, Hct and Hgb concentrations increased with time after the MMB injection and these changes were thought to be a result of hemoconcentration, secondary to dehydration following diuresis. Medetomidine exerts a diuretic effect via increasing the plasma natriuretic peptide concentration [18] and inhibiting antidiuretic hormone release in rats [17]. The fact that the animals could not drink sufficient water during the experiment could also have contributed to the hemoconcentration.…”

Comparison of the diuretic effects of medetomidine hydrochloride and xylazine hydrochloride in healthy cats

“…several factors are involved in the mechanism of this diuresis. These factors include inhibition of plasma AVP secretion from the pituitary gland, 4,5 inhibition of the ability of AVP-induced cAMP formation in the kidneys, 6 redistribution of the aquaporin-2 water channel independent of changes in vasopressin activity, 7 inhibition of renin release mediated directly by specific renal α 2 -adrenoceptors in the kidneys, 8 increase in plasma atrial natriuretic peptide concentrations, 9 inhibition of renal sympathetic activity, 10 osmotic diuresis attributable to hyperglycemia and glucosuria as a result of the inhibition of insulin release, 11 and inhibition of tubular sodium reabsorption. 12 However, the exact mechanism of the diuretic effect of α 2 -adrenoceptor agonists is still unknown.…”

Effects of pentobarbital, isoflurane, or medetomidine–midazolam–butorphanol anesthesia on bronchoalveolar lavage fluid and blood chemistry in rats

“…However, the increases in albumin and total protein concentration we found here after administration of MMB1 or MMB2 can be considered unrelated to inflammation, because these increases were observed in both untreated control rats and controls given purified water intratracheally. Medetomidine induces a transient increase in blood pressure owing to its effect on peripheral α2-adrenergic receptors (Ruskoaho and Leppäluoto, 1989;Sinclair, 2003). Therefore, the increases in BALF albumin and total protein concentrations may be due to leakage of albumin and other proteins from the blood into the alveoli during the medetomidinemediated transient increase in blood pressure.…”