Citations

To evaluate the participation of nitric oxide (NO) on pressure-induced natriuresis in pentobarbital-anesthetized dogs, renal perfusion pressure (RPP) was increased twice from 100 to 150 mmHg before and during the intrarenal administration of an NO-synthesis inhibitor, NG-nitro-L-arginine methyl ester (L-NAME), while determining changes in glomerular filtration rate (GFR), renal blood flow (RBF), and urine sodium and water excretion. Before the inhibition of NO, the increase in RPP induced diuresis (5-fold) and natriuresis (4.2-fold) with no change in RBF or GFR. However, the intrarenal infusion of L-NAME (1 microgram.kg-1.min-1) blunted the diuretic and natriuretic responses without altering RBF or GFR. The infusion of the NO synthesis precursor L-arginine prevented the inhibitory effect that L-NAME exerted on the diuretic and natriuretic responses to the increase in RPP. These results indicate that the increase in RPP stimulates NO synthesis and suggest that NO might play an important role in the control of sodium and water excretion during acute changes in RPP.

Acetylcholine (ACh) stimulates the endothelial release of prostacyclin and endothelium-derived relaxing factor (EDRF). However, the relative participation of these substances in mediating the renal effects of ACh remains undefined. To elucidate this issue, we studied the modifications of renal responses to intra-renal ACh infusion (25 ng.kg-1.min-1) produced by blocking the synthesis of EDRF and/or prostaglandins (PG) in anesthetized dogs. ACh induced a significant increase in renal blood flow (RBF) (34%), urine volume (UV) (450%), and urinary sodium excretion (UNaV)(259%), which remained unaltered after blocking the synthesis of EDRF [NG-monomethyl-L-arginine (LNMMA), 50 micrograms.kg-1.min-1 intrarenal] or PG (meclofenamate, 5 mg/kg iv). However, the simultaneous administration of meclofenamate and LNMMA prevented the ACh-induced increase in RBF and UV but not in UNaV. The concomitant infusion of L-arginine but not D-arginine prevented these blocking effects of LNMMA. It was concluded that the ACh-induced increases in RBF and UV, but not UNaV, are mediated by both PG and EDRF. The hemodynamic and diuretic effect of either one of these mediators can be fully compensated during the blockade of the other.

The effects of intrarenal infusions of calcium gluconate (10 and 100 micrograms Ca.kg-1.min-1) on renal hemodynamics and on renal excretory function were studied in anesthetized mongrel dogs. In one group, the two doses of calcium were infused for 30 min each (1 ml/min). In a second group, the same doses were administered 30 min after the start of an infusion of prostaglandin (PG) inhibitors (intrarenal indomethacin, 10 micrograms.kg-1.min-1, or intravenous bolus injection of meclofenamate, 5 mg/kg). No change with physiological significance was observed during the infusion of 10 micrograms Ca.kg-1.min-1. However, the infusion of 100 micrograms Ca.kg-1.min-1 induced increases (P less than 0.05) in glomerular filtration rate (50%), sodium excretion rate (180%), and fractional excretion of sodium (160%), with respect to control precalcium values. All these changes were prevented by the concurrent administration of PG synthesis inhibitors. Urinary PGE2 and 6-keto-PGF1 alpha increased 220 and 85%, respectively, during the infusion of 100 micrograms Ca.kg-1.min-1, but both decreased (P less than 0.05) below basal levels during the concurrent administration of PG synthesis inhibitors. The infusion of 100 micrograms Ca.kg-1.min-1 decreased (P less than 0.05) renal blood flow by 16% during the administration of PG synthesis inhibitors. These results suggest that PGs are mediating the increase in hemodynamic and excretory factors induced by the intrarenal infusion of 100 micrograms Ca.kg-1.min-1.

Data indicate significant phenotypic and genotypic overlap, plus a common pathogenesis, between two groups of inherited disorders, autosomal dominant polycystic kidney diseases (ADPKD), a significant cause of ESRD, and autosomal dominant polycystic liver diseases (ADPLD), which result in significant PLD with minimal PKD. Eight genes have been associated with ADPKD ( PKD1 and PKD2 ), ADPLD ( PRKCSH , SEC63 , LRP5 , ALG8 , and SEC61B ), or both ( GANAB ). Although genetics is only infrequently used for diagnosing these diseases and prognosing the associated outcomes, its value is beginning to be appreciated, and the genomics revolution promises more reliable and less expensive molecular diagnostic tools for these diseases. We therefore propose categorization of patients with a phenotypic and genotypic descriptor that will clarify etiology, provide prognostic information, and better describe atypical cases. In genetically defined cases, the designation would include the disease and gene names, with allelic (truncating/nontruncating) information included for PKD1 . Recent data have shown that biallelic disease including at least one weak ADPKD allele is a significant cause of symptomatic, very early onset ADPKD. Including a genic (and allelic) descriptor with the disease name will provide outcome clues, guide treatment, and aid prevalence estimates.

ObjectiveTo confirm prior findings that the larger the maximum monthly increase in solar insolation in springtime, the younger the age of onset of bipolar disorder.MethodData were collected from 5536 patients at 50 sites in 32 countries on six continents. Onset occurred at 456 locations in 57 countries. Variables included solar insolation, birth‐cohort, family history, polarity of first episode and country physician density.ResultsThere was a significant, inverse association between the maximum monthly increase in solar insolation at the onset location, and the age of onset. This effect was reduced in those without a family history of mood disorders and with a first episode of mania rather than depression. The maximum monthly increase occurred in springtime. The youngest birth‐cohort had the youngest age of onset. All prior relationships were confirmed using both the entire sample, and only the youngest birth‐cohort (all estimated coefficientsP< 0.001).ConclusionA large increase in springtime solar insolation may impact the onset of bipolar disorder, especially with a family history of mood disorders. Recent societal changes that affect light exposure (LEDlighting, mobile devices backlit withLEDs) may influence adaptability to a springtime circadian challenge.