Akira Ohishi

Status of patients who underwent uninephrectomy in adulthood more than 20 years ago

We investigated the status of patients without systemic diseases who had undergone uninephrectomy for unilateral renal diseases in adulthood more than 20 years ago at Tokyo Denryoku Hospital. There were 21 participants (mean age +/- SD, 58.6 +/- 8.0 years) who fulfilled these criteria. The average interval since nephrectomy was 27.9 +/- 6.2 years. The mean current creatinine clearance was 88.5 +/- 21.2 mL/min/1.73 m2, which is 92.9% of that in healthy age- and sex-matched controls with two kidneys. The 24-hour urine protein excretion in these patients was only slightly higher than in the controls (214 +/- 190 mg v 119 +/- 62 mg, P = NS). Age at nephrectomy, length of time with a single kidney, or sex had little effect on the remnant renal functions. There was a positive correlation between current mean arterial pressure and serum creatinine (r = 0.44, P < 0.05). Patients who developed hypertension after uninephrectomy had a family history of hypertension more frequently than those with normotension (86% v 29%, P < 0.05). We conclude that (1) renal function after compensatory hyperfiltration of more than 20 years due to uninephrectomy for unilateral renal diseases in adulthood is well maintained, although hypertension has a considerable effect on the renal functions, and that (2) family history of hypertension plays a key role in determining the incidence of hypertension even in the uninephrectomized patients.

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 Carvedilol on Renal Function and Blood Pressure in Three-Fifths Nephrectomised Spontaneously Hypertensive Rats Loaded with High Salt

Recent accumulated evidence has revealed that systemic hypertension is a risk factor contributing to acceleration of renal disease. In the clinical situation it is uncertain whether antihypertensive therapy slows the progression ofrenal disease. Since a relatively long term study is needed to clarify these facts in patients with renal disease , studies in animal models of hypertensive renal disease prompted us to investigate the relationship between systemic and glomerular pressure. In the present study, we investigated the effects of a newly developed vasodilator ,B-blocker, carvedilol, on blood pressure and renal function; serial changes in blood pressure, urinary excretion of protein and serum creatinine were measured in three-fifths nephrectomised spontaneously hypertensive rats.

Oral calcium carbonate administration ameliorates the progression of renal failure in rats with hypertension

Oral calcium supplementation is reported to have phosphate-binding and antihypertensive effects. Since both phosphate binders and antihypertensive agents are reported to attenuate renal injury, we studied the effect of oral calcium carbonate (CaCO3) administration on the course of renal deterioration using doxorubicin-induced renal failure in rats treated with deoxycorticosterone acetate and salt for 10 weeks. Rats were divided into four groups: the CaCO3 (6.0 g/kg/d) group (n = 12), the aluminum hydroxide (Al(OH)3; 6.0 g/kg/d) group (n = 11, as a phosphate-binder control), the hydralazine (10 mg/kg/d) group (n = 11, as an antihypertensive control), and the control group (n = 12). All agents were given as a mixed chow diet. Blood pressure and urinary protein excretion progressively increased in the control rats. CaCO3 and hydralazine lowered blood pressure, but Al(OH)3 did not (185 +/- 4 mm Hg, control; 160 +/- 5 mm Hg, CaCO3; 171 +/- 8 mm Hg, Al(OH)3; 156 +/- 5 mm Hg, hydralazine at week 10). Proteinuria was reduced in the rats treated with CaCO3 and Al(OH)3 compared with those without the treatment (986 +/- 86 mg/d, control; 551 +/- 54 mg/d, CaCO3; 527 +/- 31 mg/d, Al(OH)3; and 955 +/- 68 mg/d, hydralazine at week 10). Serum phosphate concentration and calcium phosphate products also were significantly lower in both the CaCO3 and Al(OH)3 groups than in the control group. At week 10, increased serum urea nitrogen, impaired renal function, and glomerular sclerosis present in the control group were significantly attenuated in both in the CaCO3 and Al(OH)3 groups.(ABSTRACT TRUNCATED AT 250 WORDS)

EFFECTS OF CICLETANINE ON THE PROGRESSION OF RENAL FAILURE IN 5/6 NEPHRECTOMIZED HYPERTENSIVE RATS

1. The effect of cicletanine, a novel antihypertensive agent with natriuretic activity, on blood pressure and progression of renal failure in 5–6 nephrectomized spontaneously hypertensive rats with salt loading was examined.