Renal physiology最新文献

The effects of a calcium channel agonist, BAY K-8644, on renin release and renal function were examined in perfused rat kidneys. BAY K-8644 increased renal vascular resistance and reduced glomerular filtration rate, sodium excretion and urine flow in a dose-dependent manner. These actions were prevented by the calcium channel blocker nifedipine. BAY K-8644 had no significant effect on basal renin secretion and failed to prevent renin stimulation by low-perfusion pressure or isoproterenol. The inhibitory effect of high-perfusion pressure on renin secretion was attenuated by the calcium entry blocker verapamil but not by nifedipine. Thus, if voltage-dependent calcium channels in the juxtaglomerular cell membrane participate in the regulation of renin release then these channels appear to be very insensitive to blockade or augmentation by 1,4-dihydropyridines.

Isolated kidney-cortical tubule suspensions and microdissected nephron segments from fed rats were used to study the action of catecholamines on gluconeogenesis. Gluconeogenesis from rat tubule suspension incubated with 5 mM pyruvate was stimulated maximally by 10(-5) M methoxamine, an alpha 1-selective agonist, and 10(-6) M noradrenaline by 29.2 +/- 5.2% (mean +/- SEM) and 32.6 +/- 2.9%, respectively. These effects were completely inhibited by 10(-7) M prazosin, a beta 1-selective antagonist. Yohimbine, an alpha 2-antagonist, also inhibited the effect, but only at a higher concentration (5 X 10(-5) M). Gluconeogenesis was not stimulated by isoproterenol, a alpha-agonist, at any concentrations between 10(-5) and 10(-7) M. With microdissected nephron segments, only the proximal tubule possessed gluconeogenic activity. Within the proximal tubule, the proximal convoluted tubule (PCT) revealed higher gluconeogenic activity than the proximal straight tubule (PST). Methoxamine at 10(-5) M stimulated gluconeogenesis in PCT, whereas in PST no increase of gluconeogenesis was observed. From these results, it can be concluded that an alpha 1-adrenergic agonist specifically stimulates renal gluconeogenesis in PCT, but not in PST.

Experiments were performed to assess the effects of nifedipine, a calcium channel blocker, on the blood pressure and bilateral renal function in 2-kidney, 1-clip, Goldblatt hypertensive rats. Hypertensive rats were prepared 4 weeks prior to the acute experiments, Nifedipine was administered intravenously into hypertensive (n = 11) and control (n = 12) rats under pentobarbital anesthesia. In hypertensive rats, nifedipine (0.02 mg/kg) reduced the mean arterial pressure from 151 +/- 5 to 135 +/- 5 mm Hg. Despite the fall of arterial pressure, there were significant increases in glomerular filtration rate (GFR) from 1.36 +/- 0.13 to 1.80 +/- 0.22 ml/min, urine flow from 7.8 +/- 1.6 to 17.0 +/- 3.8 microliter/min, and excretions of absolute and fractional sodium from 1.07 +/- 0.43 mu Eg/min and 0.50 +/- 0.15% to 2.80 +/- 0.73 mu Eq/min and 0.92 +/- 17%, respectively, in the nonclipped kidney. No significant changes in these renal indices occurred in the clipped kidney. In control rats, administration of nifedipine (0.04 mg/kg) also significantly decreased the arterial pressure from 119 +/- 4 to 110 +/- 4 mm Hg. There were slight but insignificant increases in GFR and renal excretion of sodium and water. In both groups, nifedipine produced proportionate increases in osmolar clearance and free water reabsorption. These results suggest that nifedipine enhances glomerular filtration and suppresses the reabsorption of sodium and water by the proximal tubule and/or distal nephron segments. The resulting increase in excretory function of the nonclipped kidney may, in part, contribute to the blood pressure-lowering effect of this drug.

Antisera to the streptococcal cell membrane (SCM) were evaluated for their reactivity to murine glomerular basement membrane (GBM) in four strains of mice. Animals were studied on a daily basis from birth through 3 months and weekly thereafter through 18 months. Paired animals were compared for in vivo binding of antibody versus an indirect fluorescent antibody technique on fresh kidney sections. The findings demonstrated a granular type GBM staining for all anti-SCM which were positive. Nonspecific background staining accompanied most of the indirect fluorescent antibody sections tested while being totally absent for the direct fluorescent test on tissue from in vivo challenge of the primary antibody. The in vitro testing showed tissue from young mice (0-6 days old) to be most reactive, while the strongest reactivity was seen in the age group of 10-20 days for in vivo testing. These cross-reactive antibodies, i.e., GBM-binding anti-SCM, are best evaluated by in vivo methods where tissue is taken 4 days after antiserum injection. Animals of the age range 6-8 weeks were often negative, indicating that this age range selected for many studies may not be the most favorable one via either in vitro or in vivo studies.

The macula densa is believed to function as a sensor for control of intrarenal vascular tone and renin secretion. Increases in flow rate through the loop of Henle or increases in distal tubular fluid NaCl concentration result in an increase in local vascular tone and a decrease in glomerular filtration rate, the tubuloglomerular feedback (TGF) mechanism. Increases in distal NaCl concentration are also believed to inhibit renin secretion. Evidence will be reviewed that suggests that these two processes may be activated concurrently and may share common cellular mechanisms. Similarities in the sensor step include a similar pattern of ion specificity, with both responses being relatively anion specific but showing little cation specificity. TGF responses are inhibitable by furosemide, and the renin secretion produced by furosemide seems to be in part macula densa dependent. There appear also to be common features in the effector step of both responses. Increases in intracellular calcium are implicated in both the vasoconstrictive response seen with increased macula densa NaCl concentration and in inhibition of renin secretion. Changes in cyclic AMP may play a role in the converse responses.

The volume control of the syncytium of principal cells (as opposed to the mitochondria-rich cells) is largely confined to the movement of ions and water through the basolateral membrane. The apical membrane is nearly tight to water and ions except sodium. The basolateral membrane is normally tight to chloride, but its chloride channels open if the cells swell osmotically or if the membrane is depolarized. If the epithelium has lost KCl during osmotic swelling, it is recovered by a basolateral cotransport of KNaCl2.

Autoregulatory efficiency of renal blood flow (RBF) and glomerular filtration rate (GFR) was evaluated in male Sprague-Dawley rats during interference with the renin-angiotensin system by a converting enzyme inhibitor (CEI), captopril (3 mg X h-1 X kg-1 BW). RBF and GFR were approximately 25 (p less than 0.01) and 20% (p less than 0.02) higher, respectively, in rats infused with CEI than in control rats at spontaneous renal arterial pressure (RAP). A reduction of RAP to 100 mm Hg (within the autoregulatory range) resulted in effective autoregulation of GFR and RBF in control rats. In rats given CEI, however, the autoregulation of GFR was markedly impaired. GFR decreased by 35% (p less than 0.001), while RBF remained relatively unchanged. This caused the filtration fraction to decrease from 0.33 +/- 0.01 to 0.29 +/- 0.01 (p less than 0.001). RAP had a consistent effect on the urine flow rate, even though both GFR and RBF were well autoregulated in control rats. No significant decrease in electrolyte excretion was detected within the autoregulatory range in control rats, but during converting enzyme blockade this excretion decreased progressively as RAP was reduced, and the decrease correlated well to the reduction in GFR. In summary, these results suggest that the renin-angiotensin system plays an important intrarenal role in the autoregulation of GFR, probably through an efferent arteriolar mechanism. Furthermore, it is demonstrated that the contralateral kidney efficiently compensates in urinary electrolyte excretion for an acute unilateral reduction of RAP.(ABSTRACT TRUNCATED AT 250 WORDS)

We studied factors influencing urine pCO2 minus blood pCO2 [(U-B)pCO2] in rabbits infused with sodium bicarbonate solutions. Unlike other species, the rabbit does not develop a significant (U-B)pCO2 (urine pCO2 greater than blood pCO2) after alkali or acid buffer infusion. However, intravenous acetazolamide immediately induced a significant (U-B)pCO2. The effect could not be related to the blood pH or pCO2, the urinary concentration of bicarbonate or inorganic phosphate, or to changes in plasma potassium concentration. Methazolamide was also effective in increasing (U-B)pCO2. This significant (U-B)pCO2 was present after carbonic anhydrase inhibition in rabbits subjected to chronic partial obstruction of urinary flow and in rabbits treated with 11-desoxycorticosterone acetate (DOCA). We propose that carbon dioxide is normally dissipated from the alkaline urine of the rabbit by a distal tubular mechanism, which involves catalytic conversion of carbon dioxide to bicarbonate. Inhibition of carbonic anhydrase leads to the formation of a significant (U-B)pCO2. In the rabbit, pCO2 may be an index of collecting duct acidification under certain circumstances; however, the relation of collecting duct acidification to the high (U-B)pCO2 during the inhibition of carbonic anhydrase remains to be determined.

To investigate the interaction between arginine-vasopressin (AVP) and the renal kallikrein-kinin system (KKS), urinary excretion rates of bradykinin (BK) and lysyl-bradykinin (LBK) were monitored in humans following water-loading, and in conscious diabetes insipidus (DI) rats during the infusion of AVP. In humans, the excretion rate of both BK and LBK decreased markedly 90 min after the water load. There was a close positive correlation between plasma AVP levels and urinary BK excretion, while urine flow was correlated negatively with the excretion rates of both kinins. In DI rats infusion of AVP caused a significant, reversible increase (from 14 +/- 2.8 to 35 +/- 5.1 fmol/min) in BK excretion. These results further implicate AVP in the regulation of the activity of the renal KKS.

Previous studies have shown that the clearance of lithium (CLi) is a quantitative measure of the delivery of tubular fluid to Henle's loop in rats given food with an ordinary or high sodium content, but not in rats given food with a low sodium content, because under these latter circumstances lithium is also reabsorbed to some extent in the distal nephron. The present study examines the effect of acetazolamide, hydrochlorothiazide, furosemide, and amiloride on the distal reabsorption of lithium in conscious rats with hereditary diabetes insipidus fed standard diets with medium (300 mmol Na/kg) and low (5 mmol Na/kg) sodium contents, respectively. Low sodium diet induced distal Li reabsorption, as apparent from the decrease in CLi and a fall in the urine/plasma lithium concentration ratio (U/P)Li, to below 1.0. Amiloride and furosemide abolished the distal Li reabsorption. Acetazolamide also abolished distal Li reabsorption and, in addition, it increased the fluid output from the proximal tubules. Hydrochlorothiazide was unable to abolish distal Li reabsorption.