Dopamine receptors in glomeruli and renal cortical tubules were characterized using radioligand binding and adenylate cyclase studies. The binding of [3H]haloperidol to glomeruli and tubules was rapid, saturable with time and ligand concentration, reversible, of high affinity, and demonstrated stereoselectivity and antagonist and agonist rank potency for binding to dopamine receptors. Analysis of kinetic data and Rosenthal plots in glomeruli revealed a single class of [3H]haloperidol binding sites with an apparent dissociation constant (Kd) of 6 nM and maximum receptor density (Bmax) of 0.42 pmol/mg protein. In tubules, at least two binding sites were noted, one with an apparent Kd of 38 nM and Bmax of 1.90 pmol/mg protein and another with an apparent Kd of 183 nM and Bmax of 3.50 pmol/mg protein. Dopamine and apomorphine increased adenylate cyclase in tubular membranes while no increases were noted in glomeruli. These studies suggest that glomeruli have D2 dopamine receptors, while renal cortical tubules contain the D1 dopamine receptor.

We examined 1) the potential modifications in both single nephron filtration rate (SNGFR) and the determinants of glomerular ultrafiltration, and 2) the alterations in peritubular capillary (PTC) "physical factors" that may contribute to changes in proximal tubular reabsorption (APR) after acute renal denervation (DNx). Micropuncture measurements were obtained in euvolemic Munich-Wistar rats with DNx or sham operation (sham). The content of norepinephrine in renal tissue homogenates was markedly reduced in DNx kidneys compared with sham kidneys (P less than 0.001). Mean arterial blood pressure, hematocrit, whole kidney GFR, and urinary flow rate were not different between the sham and DNx groups. Absolute urinary sodium excretion was 3 times greater in the DNx than in the sham group (P less than 0.01). SNGFR and its determinants were not statistically different in the two experimental conditions. APR was significantly reduced by approximately 25% in DNx (P less than 0.02). This reduction in APR was not accompanied by significant directional changes in peritubular capillary and renal interstitial pressures and the passive driving forces acting across the PTC-proximal tubular epithelium. These data demonstrate that elimination of renal innervation does not alter SNGFR or its determinants and suggest that the effect of denervation on APR is a primary epithelial event that occurs independent of changes in renal interstitial pressure and peritubular oncotic and hydrostatic pressures.

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.

The vascular endothelial growth factor (VEGF) family is important for establishing normal pregnancy, and related single nucleotide polymorphisms (SNPs) are implicated in abnormal placentation and preeclampsia. We evaluated the association between preeclampsia and several VEGF SNPs among Filipinos, an ethnically distinct group with high prevalence of preeclampsia. The genotypes and allelic variants were determined in a case-control study (191 controls and 165 preeclampsia patients) through SNP analysis of VEGF-A (rs2010963, rs3025039) and VEGF-C (rs7664413) and their corresponding receptors VEGFR1 (rs722503, rs12584067, rs7335588) and VEGFR3 (rs307826) from venous blood DNA. VEGF-A rs3025039 C allele has been shown to associate with preeclampsia (odds ratio of 1.648 (1.03-2.62)), while the T allele bestowed an additive effect for the maintenance of normal, uncomplicated pregnancy and against the development of preeclampsia (odds ratio of 0.62 (0.39-0.98)). VEGFR1 rs722503 is associated with preeclampsia occurring at or after the age of 40 years. The results showed that genetic variability of VEGF-A and VEGFR1 are important in the etiology of preeclampsia among Filipinos.

We report two female siblings (ages 4 and 9 years) and one 8-year-old male with the syndrome of apparent mineralocorticoid excess (AME) presenting with low renin hypertension and hypoaldosteronism. The deficiency of 11 beta-hydroxysteroid dehydrogenase results in a defect of the peripheral metabolism of cortisol (F) to cortisone (E). As a result, the serum cortisol half-life (T1/2) is prolonged, ACTH is suppressed, and serum F is normal. The specific diagnosis of the disorder was made by the decreased ratio of the urinary metabolites of E (tetrahydrocortisone, THE) and F (tetrahydrocortisol, THF). Continuous i.v. hydrocortisone administration caused an increase in blood pressure and decrease in serum potassium demonstrating the abnormal mineralocorticoid activity of cortisol in these patients. Addition of spironolactone resulted in a decrease in blood pressure, rise in serum potassium and a gradual increase in plasma renin activity. These studies suggest that an abnormality in cortisol action or metabolism results in cortisol behaving as a potent mineralocorticoid and causing the syndrome of AME.