Characterization of Alterations of Hemodynamics and Neuroendocrine Hormones in Dexamethasone Induced Hypertension in Dogs

Abstract

The serial changes in systemic and renal hemodynamics, water and electrolyte balances and various vasoactive hormones were examined in 12 conscious dogs before, during (10 days) the administration of dexamethasone (DEX: 0.5 mg/kg/day) and after the cessation of DEX. In addition, during the administration of DEX, pressor responses to angiotensin II, norepinephrine, an angiotensin II analogue, saralasin, and an alpha-1-blocker, prazosin, were studied. Abrupt elevation of blood pressure to 106 +/- 5 mmHg on Day 1 (vs. 91 +/- 6 mmHg control: P less than 0.05) associated with marked increases in total peripheral resistance (P less than 0.01) was shown in DEX treated animals. Accompanied with these changes, renal blood flow increased to 146 +/- 12 ml/min (vs. 103 +/- 8 ml/min control: P less than 0.05) on Day 1 and maintained. In contrast, the results of serial alterations in hormones could not show any significant changes except significant elevations in atrial natriuretic peptide and reductions of cortisol and arginine vasopressin. Also, marked natriuresis and diuresis were observed in DEX administration dogs. Pressor response to norepinephrine was significantly increased and administration of either saralasin and prazosin significantly reduced the blood pressure of DEX treated animals. These results in DEX-treated conscious dogs confirmed our previous findings in human and rats. Glucocorticoid-induced hypertension mainly depends on the increases in total peripheral resistance but not volume factors.

Hemodynamics of dexamethasone-induced hypertension in the rat

“…4,15 There are also reports implicating DEX in potentiating vascular pressor responsiveness to noradrenaline and/or angiotensin II in humans, 6 rats 16 and dogs. 7 Despite detecting an increase in TPR, we did not observe any significant differences in blood flow or resistance in individual renal, mesenteric or hindquarter vascular beds in this study. It is possible that the observed increase in TPR may reflect cumulative changes from a number of peripheral vascular beds, including those evaluated in this study.…”

“…14 DEX-HT in dogs was not accompanied by a significant alteration in plasma osmolality. 7 Another explanation for the increase in TPR is DEX-induced changes to vascular tone. There is increasing evidence linking deficiency in vasorelaxant nitric oxide to the pathogenesis of DEX-HT.…”

“…6 Although these are useful data depicting the hemodynamic patterns of DEX-HT, little is known about the regional flow patterns contributing to increased TPR. In dogs, DEX-HT (0.5 mg kg À1 per day) was found to be associated with increased TPR and decreased CO. 7 Whether these changes represent features necessary for the development of DEX-HT is not known. In that study, only CO, TPR and renal blood flow were evaluated, leaving other hemodynamic parameters unexamined.…”

“…7 DEX-HT in humans (3 mg per day) was associated with increased total peripheral resistance (TPR) without any change in cardiac output (CO). 6 Although these are useful data depicting the hemodynamic patterns of DEX-HT, little is known about the regional flow patterns contributing to increased TPR.…”

Association Between GLCCI1 Promoter Polymorphism (Rs37972) and Post-Transplant Hypertension in Renal Transplant Recipients

“…calcineurin inhibitor (CNI), cyclosporine, tacrolimus, or glucocorticoids) [6,8]. The mechanism of glucocorticoidinduced hypertension is known to involve the inhibition of vasodilation [9][10][11][12][13][14]. However, it remains unknown what types of patients develop post-transplant hypertension in response to glucocorticoid usage and what types do not.…”