Renal alpha-adrenoceptors and sodium excretion in the dog.

The purpose of this study was to characterize the age-dependent role of alpha-adrenergic activity on renal vascular resistance (RVR) and renal blood flow (RBF) and the role of alpha 2-receptors in sodium transport. Intrarenal infusion of phentolamine in hydropenic anesthetized pups and adult dogs increased RBF and glomerular filtration rate (GFR) only in pups. The effect was most marked in the youngest pups (15.67 +/- 0.67 days). At 1.0 micrograms X kg-1 X min-1, phentolamine increased RBF from 1.38 +/- 0.04 to 1.64 +/- 0.04 ml X min-1 X g kidney wt-1 and GFR from 0.19 +/- 0.01 to 0.23 +/- 0.01 ml X min-1 X g kidney wt-1. Absolute (UNaV) and fractional (FENa) sodium excretions increased in all animals, but mean percent increases were greatest in adult dogs. Intrarenal yohimbine infusion in adult dogs (10-100 micrograms X kg-1 X min-1) produced a dose-related increase in UNaV and FENa without affecting RBF and GFR. UNaV increased from 0.22 +/- 0.05 to 0.54 +/- 0.12 mueq X min-1 X g kidney wt-1 and FENa increased from 0.32 +/- 0.05 to 0.63 +/- 0.06% at the dose of 100 micrograms X kg-1 X min-1. These studies confirm a modest role for alpha-adrenoreceptors in the high RVR characteristic of newborn pups and provide evidence for a role of alpha 2-adrenoceptors in the renal transport of sodium; the extent of the contribution of renal alpha-adrenergic system could not be tested in this experiment.

Dopamine receptors in the proximal tubule of the rabbit.

Our laboratory has characterized dopamine receptors in glomeruli and tubular homogenates. Since the heterogeneity of kidney homogenates limits the interpretation of these studies, the [3H]haloperidol binding site and adenylate cyclase sensitivity to dopamine were studied in the isolated proximal convoluted tubule and pars recta of the rabbit kidney. [3H]Haloperidol binding sites were saturable, stereoselective, and of high affinity. The apparent dissociation constant was 31.5 X 10(-9) M (+/- 8.5) and the maximum receptor density was 0.31 X 10(-15) M (+/- 0.08) per millimeter. In pars recta specific binding was 53% of total [3H]-haloperidol binding. Dopamine stimulated adenylate cyclase activity in a dose-related manner, which was inhibited by cis-flupenthixol but not by trans-flupenthixol or (-)-propranolol. Moreover, the stimulatory effect of the dopamine 1 (D1) agonist SKF 82526 on adenylate cyclase activity was blocked by the D1 antagonist SCH 23390. Dopamine receptors in the proximal convoluted tubule appear to be of the D1 subtype since they are linked to stimulation of adenylate cyclase. This is further substantiated by the stereoselectivity for (+)-sulpiride (a D1 antagonist), which had a greater affinity for the [3H]haloperidol binding site than (-)-sulpiride (a D2 antagonist).

Autoantibodies in minimal change nephrotic syndrome.

The presence of low level antibody (AAb) activity and circulating immune complexes (CIC) were studied in 17 patients with minimal change nephrotic syndrome (MCNS). Study groups include 12 MCNS without mesangial deposits (Group I) and 5 MCNS with mesangial deposits (Group II). In Group I reactivity against normal tissue antigens was demonstrated (kidney tubular microsomal antigen - 8, smooth muscle - 5, gastric cell - 5). In Group II reactivity against kidney basement membrane was demonstrated in all five patients. CIC were detected in eight (Group I - 6, Group II - 2). Dissociation of the CIC showed that they all contained antibodies with a corresponding autoantibody activity which could be removed by prior incubation with their complexed antigen. The presence of these AAb's and their formation of CIC may indicate their role in initiating a primary immunological insult to the kidney.

Gold-associated nephropathy.

Renal biopsy specimens from 11 cases of gold-associated nephropathy were studied by light, immunofluorescence, and electron microscopy. Seven biopsy specimens disclosed the typical glomerular lesions of membranous nephropathy. Four cases disclosed other patterns of glomerular injury, including minimal-change nephrotic syndrome. Although a membranous pattern of immune complex deposition is the most frequent type seen in gold nephropathy, our data indicate that other patterns of immune complex deposition may occur in renal biopsy specimens of patients receiving gold therapy.

The influence of age on acute renal toxicity of uranyl nitrate in the dog.

The influence of age upon uranyl nitrate (UN) induced acute renal failure (ARF) was evaluated in 30 canine puppies 1-2 wk and 3-5 wk old. Renal function and morphologic studies were performed 2 h (initiation phase) and 24 h (maintenance phase) after UN administration. Age-matched controls received vehicle alone. Administration of UN to 1-2-wk-old puppies produced no changes in whole kidney glomerular filtration rate (GFR), despite a significant reduction in renal plasma flow (RPF) (P less than 0.01). In contrast, during the maintenance phase, GFR was 60% lower than in the control group (P less than 0.02) whereas values for RPF were nearly identical to control values. In 3-5-wk-old puppies the magnitude of response to the heavy metal was much greater and GFR was nearly completely suppressed during the maintenance phase. This major alteration of GFR was independent of changes in RPF, because RPF remained similar to control values. Morphologic alterations consistent with the nephrotoxic effects of UN were observed in the proximal tubules of the most differentiated nephrons. These age-related morphologic alterations correlated well with the functional response (GFR) observed after UN administration, i.e., a proportionately greater degree of both morphologic and functional alterations followed the administration of the heavy metal in the oldest group of puppies.

Alpha-adrenoceptors in the developing kidney.

The maturation of renal alpha-adrenoceptors was investigated in dogs. Alpha-adrenoceptors were characterized by radioligand binding using the alpha-1-adrenergic antagonist, [3H]-WB-4101. In renal plasma membranes obtained from the outer cortex of neonates, the binding of the ligand was rapid, reversible, of high affinity, saturable, and stereoselective. The competition studies with adrenergic agonists and antagonists were indicative of alpha-receptors. In puppies less than 1-w-old, the binding affinity of [3H]-WB-4101 (Kd = 0.638 +/- 0.17 nM) was greater than 3-5 week-old puppies (Kd 1.573 +/- 0.315 nm); (P less than 0.05), but receptor number was similar (63.75 +/- 19.1 versus 79.10 +/- 5.99 fmole/mg protein). No consistent specific binding could be demonstrated in plasma membranes obtained from inner cortex of medulla. In the adult dog, no consistent specific binding could be demonstrated for plasma membranes obtained from any region of the kidney. These studies indicate that during maturation there is a decrease in alpha-adrenoceptor density and affinity in membranes from the outer cortex of the kidney.

Ontogeny of myocardial adrenoceptors II. Alpha adrenoceptors.

The maturation of myocardial alpha adrenoceptors was investigated in dogs. Alpha adrenoceptors were characterized by radioligand binding using [3H]-WB4101. In neonatal cardiac membranes, the binding of the ligand was rapid, reversible, of high affinity, saturable and stereoselective. The competition studies with adrenergic agonists and antagonists were indicative of alpha adrenoceptors. In adult dog cardiac membranes, consistent specific binding of the ligand could be demonstrated. These studies indicate that there is a decrease in alpha adrenergic receptor density of canine cardiac membranes during maturation.

Hyperlipidemia in children with chronic renal insufficiency.

Total serum cholesterol, phospholipids, and triglyceride levels, lipoprotein fractionation, and plasma parathormone levels were measured in a group of 31 nonnephrotic children with various levels of renal function and on hemodialysis. Group A served as controls and consisted of eight healthy children with glomerular filtration rate (GFR) greater than 110 ml/min/1.73 m2. Group B consisted of six children with GFR on 60 to 95 ml/min/1.73 m2. Group C consisted of nine children with GFR of 10 to 40 ml/min/1.73 m2, and group D consisted of eight children on maintenance hemodialysis with GFR of 0 to 5 ml/min/1.73 m2. Among the groups, there were no significant differences in total serum cholesterol and phospholipid levels. A significant (P less than 0.05) increase in triglyceride levels was observed in patient groups C and D. Lipoprotein fractionation revealed a significant increase (P less than 0.05) in the pre-beta lipoprotein levels (very low density lipoproteins) in patients in groups D with 63% of these patients demonstrating a type IV lipoprotein pattern. There were no significant differences observed in the beta lipoproteins (low-density lipoproteins). However, the alpha lipoproteins (high-density lipoproteins) decreased significantly (P less than 0.05) in patients whose GFR was below 40 ml/min/1.73 m2 (group C) as well as patients in group D. Absolute plasma parathormone levels did not significantly correlate with serum triglyceride levels did not significantly correlate with serum triglyceride levels and remained normal until after the onset of hemodialysis when they increased significantly in all patients.

Variability of anti-GBM binding in hereditary nephritis.

Anti-GBM staining by indirect immunofluorescence microscopy was performed on renal biopsies from 64 patients with a variety of diseases in which no in vivo bound immunoglobulin or complement components were identified by direct immunofluorescence microscopy. The glomeruli of all of the entities examined bound anti-GBM antibodies except for four of nine cases of hereditary nephritis of the Alport-type. The absence of anti-GBM staining was found to correlate with the severity of GBM splitting identified by electron microscopy.

A short communication. Congenital renal alkalosis.

Patients with idiopathic hypokalemic metabolic alkalosis and hyperrenienmia have been lumped under the heading of Bartter's syndrome. However, the clinical picture is not totally uniform. Recently, Gullner et al. described a familial disorder with hypokalemic metabolic alkalosis, hyperreninemia, and aldosteronism, but without juxtaglomerular hyperplasia. They suggested that this family had a condition other than Bartter's syndrome. The present report details the followup from infancy to adulthood of a patient with hypokalemic metabolic alkalosis, salt wasting, and hyperreninemia, but with normal aldosterone level and without juxtaglomerular hyperplasia. The authors suggest that this new condition be termed renal alkalosis. The studies suggest that the distal tubular reabsorptive capacity was defective in this patient.

Autoregulation of renal blood flow in the puppy.

The ability of the immature kidney to autoregulate blood flow was investigated. Renal blood flow was measured by electromagnetic flowmeter. In six puppies, selective blockade of the intrarenal effects of angiotensin II (AII) by [1-sarcosine, 8-alanine]angiotensin II (anti-AII) administered into the renal artery did not change renal blood flow. During selective renal AII blockade, intravenous AII raised perfusion pressure from 76 +/- 2 to 100 +/- 6 mmHg. Renal blood flow increased from 1.59 +/- 0.29 to 1.98 +/- 0.59 ml/g kidney per min, but returned to control levels within 40 s in spite of persistent arterial pressure elevation. In another group of seven puppies, renal blood flow remained constant despite reduction of renal perfusion pressure by aortic constriction to 60 mmHg. In two of these seven puppies intrarenal anti-AII did not abolish autoregulation. Autoregulation of renal blood flow occurs in the puppy and is not influenced by inhibition of angiotensin. The renin-angiotensin system does not appear to be involved in the normal regulation of renal blood flow in the puppy.