Yo Kageyama

Oral calcium treatment lowers blood pressure in renovascular hypertensive rats by suppressing the renin-angiotensin system.

The effects of calcium supplementation on blood pressure and its mechanisms were investigated in two-kidney, one clip renovascular hypertensive rats. Two series of experiments were performed: one was begun just after renal artery constriction, the other after the onset of hypertension. Calcium supplementation significantly attenuated the development of hypertension (systolic blood pressure: 183 +/- 8 vs 130 +/- 2 mm Hg) and was found to abate existing renovascular hypertension (systolic blood pressure: from 183 +/- 8 to 151 +/- 4 mm Hg). Calcium treatment did not cause significant alterations in fluid intake, urine volume, or urinary sodium excretion in either study. However, increased plasma renin activity and plasma aldosterone concentration were suppressed to the basal levels at the end of 3 weeks of calcium treatment (14 +/- 3 vs 8 +/- 2 ng angiotensin I/ml/hr; 530 +/- 50 vs 380 +/- 40 pg/ml). Blood pressure of calcium-treated renovascular hypertensive rats responded poorly to blockade of the renin-angiotensin system with captopril injection and angiotensin II analogue (saralasin) infusion. Further, in rats with chronic established renovascular hypertension, calcium treatment attenuated the enhanced pressor response to norepinephrine, but not to angiotensin II. These results suggest that the blood pressure-lowering actions of calcium supplementation are related primarily to suppression of renin secretion and secondarily to alteration of pressor response to norepinephrine in two-kidney, one clip renovascular hypertensive rats.

Different effects of low and high doses of endothelin on haemodynamics and hormones in the normotensive conscious dog.

The effects of low-dose endothelin on systemic haemodynamics and vasoactive hormones were examined in conscious dogs. In addition, we examined the effects of endothelin on pressor responses to noradrenaline and angiotensin II and the baroreflex regulation of heart rate in conscious dogs. Continuous infusion of 40 fmol/kg per min endothelin for 40 min induced a mild but significant reduction in mean arterial pressure from 89.1 +/- 1.7 to 82.7 +/- 2.0 mmHg (P less than 0.05), associated with decreases in total peripheral resistance 20 min later. A 400 fmol/kg per min dose of endothelin, on the other hand, induced a gradual elevation of mean arterial pressure from 89.2 +/- 2.3 to 96.8 +/- 2.0 mmHg (P less than 0.05), associated with increases in total peripheral resistance over 30 min. The 40 fmol/kg per min dose of endothelin infusion induced a significant reduction in plasma arginine vasopressin (AVP; P less than 0.05) and elevations of plasma atrial natriuretic peptide (ANP; P less than 0.05), plasma prostaglandin E2 (PGE2; P less than 0.05) and plasma 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha; P less than 0.05). The 400 fmol/kg per min dose produced elevations of AVP, ANP, PGE2 and 6-keto-PGF1 alpha (P less than 0.05). Pressor responses to noradrenaline and angiotensin II were significantly attenuated during continuous infusion of 40 fmol/kg per min endothelin, whereas 400 fmol/kg per min endothelin did not induce any significant changes compared with the control. Furthermore, baroreflex sensitivity was attenuated with 40 fmol/kg per min endothelin but did not show any significant changes at 400 fmol/kg per min.(ABSTRACT TRUNCATED AT 250 WORDS)

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

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.

Effects of calcium loading on blood pressure in spontaneously hypertensive rats: attenuation of the vascular reactivity

The effects of oral calcium loading on the blood pressure of spontaneously hypertensive rats (SHR) (n = 20) and age-matched normotensive Wistar-Kyoto rats (WKY) (n = 16) were investigated. Calcium loading was performed by adding 1.5% CaCl2 (Calcium chloride) to the drinking water. Calcium loading attenuated the development of hypertension in the SHR but not in the WKY, and at the end of a 3 week experiment, systolic blood pressure was 171+2 vs 197+3 mmHg (P less than 0.01). In spite of this reduction of blood pressure, there were no significant changes in sodium-water balance, plasma levels of norepinephrine and epinephrine, plasma renin activity, plasma aldosterone concentration and serum electrolytes due to the calcium treatment. On this basis, the depressor mechanism of calcium loading in the SHR was studied by observing the pressor response to norepinephrine and the vascular reactivity to norepinephrine in hind limb perfusion. It was found that both the pressor response and the vascular reactivity were significantly attenuated by the calcium treatment in the SHR but not in the WKY. These results suggest that the antihypertensive effects of calcium treatment in SHR may depend mainly on attenuation of the vascular reactivity.

Central nervous system mediates an antihypertensive property in glucocorticoid hypertension in dogs

Objective: To determine whether the central nervous system has a pressor or a depressor role in glucocorticoid-induced hypertension. Methods: Intracerebroventricular dexamethasone or its receptor antagonist, RU 38486, was administered in 20 trained conscious dogs. In addition, intracerebroventricular RU 38486 was administered in dogs treated with oral dexamethasone. Results: Intracerebroventricular dexamethasone induced a dose-related reduction in blood pressure accompanied by decreased heart rate and cardiac output. In contrast, intracerebroventricular RU 38486 caused a slight but not significant elevation in blood pressure. Total peripheral resistance showed no significant change throughout the treatment with dexamethasone or RU 38486. In contrast, oral dexamethasone caused significant elevation of blood pressure associated with increased total peripheral resistance and reduced heart rate. In hypertensive dogs treated with oral dexamethasone, intracerebroventricular RU 38486 elicited a more severe form of hypertension accompanied by an attenuation of the heart rate and a reduction in cardiac output. Intracerebroventricular dexamethasone induced a significant reduction in plasma levels of adrenocorticotrophic hormone, cortisol, arginine vasopressin and noradrenaline. In addition, simultaneous central administration of RU 38486 with intracerebroventricular dexamethasone blocked the reduction in blood pressure and heart rate completely. Conclusion: The present data strongly suggest that endogenous glucocorticoid in the central nervous system may not have a role in the regulation of systemic haemodynamics and hormones under resting conditions, but does play an important part during the glucocorticoid excess state, for example glucocorticoid hypertension caused by oral treatment with dexamethasone. The glucocorticoid in the central nervous system opposed the elevation of blood pressure in glucocorticoid-induced hypertension by attenuating the reduction in heart rate and cardiac output via direct stimulation of glucocorticoid receptors in the brain.

Central and Peripheral Contributions of the Renin-Angiotensin System in Two Models Experimental Hypertension in Rats

To examine the relationships between the central and peripheral renin angiotensin system in normotensive Wistar Kyoto (WKY) rats, two-kidney, one-clip Goldblatt renovascular hypertension (RVH), spontaneously hypertensive rats (SHR), SQ 14225 (captopril) was administered intraventricularly (IVT) and intravenously (IV) in the alternative manner and their combination. Also, the effects of IVT captopril on the peripheral sympathetic nervous system were evaluated using an intravenous injection of prazosin. IVT captopril induced a significant reduction of blood pressure in both types hypertensive rats but not in normotensive rats. Greater depressor effects of IV captopril not IV prazosin following IVT captopril were observed in RVH compared to those in SHR. These results indicate that the pressor action of the brain renin angiotensin system is closely related with the sympathetic nervous system in hypertensive conditions and that these functions are independent from the peripheral renin angiotensin system. Furthermore, their roles were different in different types of experimental hypertension in rats.