Kazutomo Ujiie

Immunohistochemical localization of V2 vasopressin receptor along the nephron and functional role of luminal V2 receptor in terminal inner medullary collecting ducts.

We investigated immunohistochemical localization of V2 vasopressin receptor along the nephron using a specific polyclonal antibody. Staining was observed in some of thick ascending limbs and all of principal and inner medullary collecting duct (IMCD) cells. Not only basolateral but also luminal membrane was stained in collecting ducts, especially in terminal IMCD (tIMCD). To learn the functional role of luminal V2 receptor in tIMCD, we studied the luminal effects of arginine vasopressin (AVP) on osmotic water permeability (Pf), urea permeability (Pu), and cAMP accumulation using isolated perfused rat tIMCD. In the absence of bath AVP, luminal AVP caused a small increase in cAMP accumulation, Pf and Pu, confirming the presence of V2 receptor in the lumen of tIMCD. In contrast, luminal AVP inhibited Pf and Pu by 30-65% in the presence of bath AVP by decreasing cAMP accumulation via V1a or oxytocin receptors and by an unknown mechanism via V2 receptors in the luminal membrane of tIMCD. These data show that V2 receptors are localized not only in the basolateral membrane but also in the luminal membrane of the distal nephron. Luminal AVP acts as a negative feedback system upon the basolateral action of AVP in tIMCD.

Role of Urinary Arginine Vasopressin in the Sodium Excretion in Patients With Chronic Renal Failure

Patients with chronic renal failure show almost equal levels of sodium excreted in the urine as healthy subjects through an increase of the fractional excretion sodium (FE(Na)). The mechanisms of this adaptation, however, are unknown. Recently, urinary arginine vasopressin (AVP) has been shown to inhibit the antidiuretic action of plasma AVP in the collecting ducts of rabbits and rats. In this article, the roles of plasma and urinary AVP are examined with other hormones in the sodium excretion of 57 patients with chronic renal disease. The fractional excretion of AVP, plasma atrial natriuretic peptide (ANP) and endothelin-1 (ET-1), urinary ET-1, and FE(ET-1) correlated with the decrease of creatinine clearance (Ccr). Multiple and stepwise regression analyses showed that FE(AVP) is the major dependent determinant for FE(Na) (adjusted r2 = 0.78). These results suggest that the increase of AVP excretion per remaining nephron could be a cause of the increase of FE(Na) in patients with renal failure. Although plasma AVP works as an antidiuretic hormone, urinary AVP serves as an intrinsic diuretic, especially in patients with chronic renal failure.

Decreased Lithium Clearance in Patients with Hyperthyroidism

Lithium clearance was studied to investigate proximal tubular function in patients with hyperthyroidism (n = 10) and control subjects (n = 7). Patients with hyperthyroidism showed significantly reduced fractional excretion of lithium (FELi) compared with control subjects (15.0 +/- 1.5%, n = 10, vs. 23.7 +/- 0.6%, n = 7, means +/- SE, p < 0.001). The reduced FELi of the hyperthyroid state was reversed toward control values with treatment by antithyroid drugs (12.6 +/- 2.6 toward 26.8 +/- 2.5% for 5 patients, means +/- SE). Tubular reabsorption of phosphate (TRP) was significantly increased in hyperthyroid patients compared with control subjects (96.1 +/- 0.7 vs. 87.5 +/- 0.7%, p < 0.001), and it returned to control values after the treatment. Our data demonstrate that lithium clearance is decreased and TRP is increased in patients with hyperthyroidism, which suggests that proximal tubular reabsorption of sodium and TRP is increased in hyperthyroidism.

Angiotensin-Converting Enzyme Activity as a Prognostic Factor in Acute Renal Failure

We evaluated serum angiotensin-converting enzyme (ACE) activity and thyroid function to determine the importance as prognostic factors in acute renal failure (ARF). Among 37 ARF patients, 24 survived (recovered group) and 13 died (lethal group). Both serum thyroxine (T4) level and ACE activity were lower in ARF as a whole group (n = 37) than normal control group (n = 27, p less than 0.01). Both serum T4 level and ACE activity in lethal group (n = 13) were significantly lower than those of the recovered group (n = 24, p less than 0.01). Serum ACE activity but not serum T4 level was significantly related to the prognosis of ARF (p less than 0.02, Mantel-Haenszel analysis). This suggests that lowered serum T4 levels are not a specific indicator of ARF, but lowered ACE activity is significantly related to the prognosis of the patient in ARF. Serum ACE activity seems to be one of several clinically useful prognostic indicators in ARF.

Effects of Kinin on Electrolytes Transport and Regulation of Kininase Activity in Distal Nephron Segments of the Rat

It is generally recognized that the cortical collecting duct plays a major role in the fine control of renal sodium excretion, and thus in the regulation of extracellular fluid volume. Several lines of evidence point to the cortical collecting duct as a possible site of kinin action on sodium transport. First, both kallikrein1-3 and kininogen4 have been localized to the collecting duct system. Second, high-affinity binding sites for bradykinin have recently been localized to the cortical and outer medullary collecting ducts5. Third, kinins have a marked inhibitory effect on vasopressin-stimulated water permeability in the isolated, perfused cortical collecting duct of the rabbit. First part of our studies is to investigate whether bradykinin directly affects net sodium transport in the cortical collecting duct of the rat using the isolated, perfused tubule technique.

Effects of Mineralocorticoid on Kininase Activity Along the Distal Nephron Segments of the Rat

The kallikrein-kinin system is known to have natriuretic action in the kidney. What is the rate limiting factor in the action of kinin? Is that the kallikrein activity, kininogen concentration, or kininase activity? There are discrepancies between urinary kallikrein activity and urinary kinin excretion in some reports. Kininogen may not be the rate limiting factor in usual condition because kininogen could be measured in the final urine. In this meaning, kininase can be considered as potential candidate as the rate limiting factor in the kallikrein-kinin system of the kidney.