Kazuhisa Ohishi

Functional impairment of renal afferent arteriolar voltage-gated calcium channels in rats with diabetes mellitus.

Experiments were performed to test the hypothesis that diabetes mellitus is associated with impaired afferent arteriolar responsiveness to opening of voltage-gated calcium channels. Diabetes was induced by injection of streptozocin (65 mg/kg, i.v.) and insulin was administered via an osmotic minipump to achieve moderate hyperglycemia. Sham rats received vehicle treatments. 2 wk later, the in vitro blood-perfused juxtamedullary nephron technique was used to allow videomicroscopic measurement of afferent arteriolar contractile responses to increasing bath concentrations of either Bay K 8644 or K+. Baseline afferent arteriolar diameter in kidneys from diabetic rats (26.4+/-1.2 microm) exceeded that of Sham rats (19.7+/-1.0 microm). Bay K 8644 evoked concentration-dependent reductions in afferent diameter in both groups of kidneys; however, arterioles from Sham rats responded to 1 nM Bay K 8644 while 100 nM Bay K 8644 was required to contract arterioles from diabetic rats. The EC50 for K+-induced reductions in afferent arteriolar diameter was greater in diabetic kidneys (40+/-4 mM) than in kidneys from Sham rats (28+/-4 mM; P < 0.05). In afferent arterioles isolated by microdissection from Sham rats and loaded with fura 2, increasing bath [K+] from 5 to 40 mM evoked a 98+/-12 nM increase in intracellular Ca2+ concentration ([Ca2+]i). [Ca2+]i responses to 40 mM K+ were suppressed in afferent arterioles from diabetic rats (delta = 63+/-5 nM), but were normalized by decreasing bath glucose concentration from 20 to 5 mM. These observations indicate that the early stage of insulin-dependent diabetes mellitus is associated with a functional defect in afferent arteriolar L-type calcium channels, an effect which may contribute to suppressed afferent arteriolar vasoconstrictor responsiveness and promote glomerular hyperfiltration.

Glomerular Refractoriness to Contractile Stimuli in Rabbits Recovering from Ischemic Acute Renal Failure

The present work was performed on uninephrectomized rabbits recovering from ischemic acute renal failure (ARF) in an attempt to elucidate whether or not intraglomerular events are a determinant factor in the development of resistance to ARF. 14 days after a 2-hour clamping of the renal artery (the recovery phase), the animals did not show resistance to an additional ischemia. On the other hand, glomeruli derived from normal kidneys displayed a contractile response to angiotensin II, arginine vasopressin or norepinephrine in Eagles minimum essential medium, whereas glomeruli from rabbits recovering from ischemic ARF were refractory to the vasoconstrictor agents. The findings suggest that glomerular refractoriness to contractile stimuli does not provide resistance to an additional renal ischemia in the ischemic model of ARF.

Impaired water excretion in a hyponatremic patient following thyroidectomy: Causal role of glucocorticoid deficiency.

We evaluated the causal role of glucocorticoid deficiency in the hyponatremia that developed in a 57-year-old Japanese man with hypothyroidism following the performance of a total thyroidectomy for laryngeal cancer. The plasma concentration of vasopressin (1.78 pg/ml) was not suppressed in the presence of hyponatremia (125 mEq/l). The urinary excretion of sodium was increased, and the plasma renin activity and plasma aldosterone concentration were suppressed. The infusion of hypertonic saline increased the plasma osmolality, but not the plasma concentration of vasopressin. An oral water load (20 ml/kg of body weight) did not suppress the plasma vasopressin level or induce diuresis. Pretreatment with hydrocortisone normalized the response of plasma vasopressin to the water load was well as the diuretic response during the hypothyroid state. The urinary exretion of 17-hydroxycorticosteroids was below normal in the hypothyroid state in the face of normal serum cortisol concentration. The correction of the hypothyroidism returned these abnormalities to normal. A disturbed metabolism of glucocorticoid may have been responsible for the hyponatremia and disturbance in plasma vasopressin regulation observed in this hypothyroid patient.

Dominant effect of supplemented-sucrose on the low protein diet-induced increase in blood pressure of Sprague-Dawley rats.

A low-protein diet (LPD) is known to affect the regulation of hemodynamics, and could contribute to the genesis of hypertension. We investigated the mechanism for the LPD-induced elevation of blood pressure in 52 Sprague-Dawley rats. Rats fed the LPD for 8 weeks showed a significantly higher blood pressure than those fed on a normal-protein diet (NPD) when the LPD included sucrose as a predominant component of carbohydrate (LPD with a high sucrose content, 135 ±2 mmHg; NPD, 124 ±2 mmHg; p<0.05). However, LPD with a low sucrose content, in which corn starch was the main component of carbohydrate, did not have a hypertensive effect (125 ±2 mmHg). Urinary epinephrine and norepinephrine excretion was significantly higher in the LPD high-sucrose group than in the NPD and LPD low-sucrose groups, and there was a significant positive correlation between urinary norepinephrine excretion and systolic blood pressure. Urinary nitric oxide excretion was no different between these groups, and 2 % L-arginine administration exerted no antihypertensive effect on the LPD-induced elevation of blood pressure. Sodium restriction also did not attenuate the LPD-induced elevation of blood pressure. These results suggest that the effect of LPD on blood pressure could be interpreted as the effect of the high sucrose content supplemented to the LPD rather than the direct effect of protein restriction, and that the stimulation of sympathetic nervous activity was associated with this elevation of blood pressure.

Case of human immunodeficiency virus infection presenting as a tip variant of focal segmental glomerulosclerosis: A case report and review of the literature

The incidence of the collapsing variant of focal segmental glomerulosclerosis (FSGS) as a human immunodeficiency virus (HIV)-associated nephropathy has reduced since the introduction of antiretroviral therapy (ART). However, the incidence of other variants of FSGS, except for the collapsing variant, is increasing, and its therapeutic strategies remain uncertain. A 60-year-old HIV infected man in remission with ART was admitted for progressive renal insufficiency and nephrotic-ranged proteinuria. Renal biopsy revealed a tip variant of FSGS and his clinical manifestations resolved with corticosteroid therapy. HIV infected patients might develop non-collapsing FSGS, including tip variant of FSGS and corticosteroid therapy might be effective for them. A renal biopsy might be essential to determine the renal histology and to decide on corticosteroid therapy.

Heterogenous Responses to Vasoactive Substances of Canine Superficial and Juxtamedullary Afferent Arterioles

It is well known that there are structural and functional differences between superficial and juxtamedullary nephrons. The size of glomeruli and the diameter of afferent arterioles are lager in juxtamedullary nephrons than in superficial nephrons. Also,the single nephron glomerular filtration rate (SNGFR) in the juxtamedullary nephron is usually 1.5 to 2.5 times greater than in the superficial nephron.2,3