Renal physiology最新文献

The purpose of the present experiments was to determine the renovascular effects of the adenosine agonists N-ethyl-carboxamide adenosine (NECA), N6-cyclohexyl adenosine (CHA) and 2-chloro adenosine (2-CLA). The diameter of pre- and postglomerular vessels in the split hydronephrotic kidney of Inactin-anesthetized rats was measured by in vivo television microscopy. All metabolically stable adenosine agonists were topically applied into the renal tissue bath. NECA, a preferential A2 adenosine receptor agonist, induced dose-dependent marked pre- and slight postglomerular vasodilation except for a small constrictory effect on the afferent arteriole near the glomerulus. Application of CHA, a selective A1 adenosine receptor agonist, led to a vasoconstriction of all preglomerular vessels, the extent of which was greatest at the most distal segment of the afferent arteriole. 2-CLA, a nonselective agonist, produced a small decrease in diameter in all preglomerular vessels, a marked constriction of the afferent arteriole at sites near the glomerulus, and a slight dilation of postglomerular vessels. Glomerular blood flow (GBF) was increased by NECA, and decreased by CHA and 2-CLA. The effects of CHA in reducing GBF were greater than those of 2-CLA. From these experiments it is concluded that vascular A1 and A2 adenosine receptors are present in the kidney and that activation of A1 receptors is associated with preglomerular vasoconstriction only, whereas activation of A2 receptors mediates pre- and postglomerular vasodilation with a lack of vasodilatory response of the distal afferent arteriole. Furthermore, these data indicate that nonselective occupation of both receptor subclasses is associated with marked vasoconstriction of the afferent arteriole and little vasodilation of the efferent arteriole.

Osmotic diuresis occurs, if nonreabsorbed solutes such as mannitol impair the reabsorption of water. The reduced reabsorption of volume affects in turn the reabsorption and excretion of solutes. Thus, mannitol leads to modest impairment of proximal tubular reabsorption not only of water, but as well of electrolytes (Na, Cl, K, Pi, Ca, but not Mg), urea, and uric acid. Infusion of hypertonic mannitol increases renal blood flow and the glomerular filtration rate of superficial nephrons. The increased perfusion of medulla leads to wash out of medullary hypertonicity. The decline of medullary osmolarity leads to a marked impairment of water reabsorption in descending limbs and possibly to moderate impairment of NaCl, Ca, and Mg reabsorption in the ascending limbs of Henle's loop. In the collecting duct, inhibition is marked of water and urea reabsorption and modest of NaCl reabsorption. A number of open questions remain, such as the mechanisms underlying decrease of renal vascular resistance, increased proximal tubular reabsorption of magnesium, or impaired NaCl reabsorption in thick ascending limbs.

Amiloride, triamterene, and the spirolactones are potassium-sparing diuretics which act on the distal parts of the nephron, from the late distal tubule to the collecting duct. In these segments, active sodium reabsorption occurs through the following mechanism: sodium ions enter the cell through specific channels present in the luminal membrane and are extruded out of the cell into the peritubular medium by a sodium-potassium exchange pump, the Na-K-ATPase. Amiloride in micromolar concentrations reduces the sodium transport by blocking the luminal membrane sodium channel. Triamterene has a similar effect, although with a lower affinity; the available studies do not allow to determine if an inhibitory effect of triamterene on the Na-K-ATPase plays an additional role in its diuretic action. The spirolactones are competitive inhibitors of aldosterone, the mineralocorticoid hormone which promotes sodium reabsorption by increasing both the number of active sodium channels in the luminal membrane and the number of active Na-K pumps in the peritubular membrane. By the inhibitory effect on the electrogenic sodium transport, amiloride, triamterene, and the spirolactones decrease the lumen-negative transepithelial potential difference. This reduces the driving force for potassium movement into the tubular lumen and thus decreases potassium excretion.

This study evaluates the direct effects of verapamil and furosemide infused into the unilateral renal artery on renal function and the renin secretion rate in renal vein-catheterized rabbits. Catheterization did not alter the renal function parameters of the kidney. Verapamil and furosemide increased renal blood flow, urine flow, and urinary sodium, potassium and chloride excretions confined to the infused kidney. Verapamil increased the glomerular filtration rate and free water clearance. The renin secretion rate was increased by furosemide but not by verapamil. The present study shows that the technique is applicable to renal function studies in which unilateral renal arterial infusion of the agents studied is required. The contralateral kidney can be a reliable control for the infused kidney. It also provides a useful technique for the study of renin release in rabbits.

The effects of administered thromboxanes on the intact, normal rat kidney were studied. Euvolemic male rats received intraarterial infusions of thromboxane B2 (TXB2) and the stable thromboxane A2 analog (U46619) and the effects on renal function were investigated, using glomerular micropuncture and whole-kidney clearance techniques. Both TXB2 and U46619 were renal vasoconstrictors and lowered GFR by reducing renal plasma flow rate; U46619 was much more potent that TXB2. Neither agent caused any marked change in the glomerular capillary ultrafiltration coefficient (Kf). Thus in the rat, the thromboxanes reduce filtration rate by increasing renal vascular resistance and without exerting a marked influence on Kf.

In the present study the possible role of endogenous prostaglandins in modulating the renal effects of angiotensin II was investigated in the isolated perfused rat kidney. Angiotensin II (5 ng/ml) caused both an increase in prostaglandin E2 synthesis and an increase in renal vascular resistance, as well as an increase in perfusate flow rate and glomerular filtration rate. Filtration fraction did not change. Inhibition of prostaglandin synthesis did not influence these effects of angiotensin II. In addition, angiotensin II caused natriuresis and to a lesser degree kaliuresis. These effects were independent of intrarenal hemodynamic effects. Inhibition of renal prostaglandin synthesis did not have any effect on the angiotensin-induced natriuresis. We conclude that the natriuretic effect of angiotensin II is independent of renal prostaglandin synthesis.

The possible mediation of the endogenous prostaglandin and kallikrein-kinin systems of changes in renal function induced by furosemide was studied in anesthetized rats. Increasing doses of furosemide infusion (0.03, 0.1, and 0.3 mg/kg/min) caused dose-related diuresis, natriuresis, kaliuresis, and decreased renal blood flow and urinary osmolality without any significant changes in mean arterial blood pressure. Pretreatment with the prostaglandin synthetase inhibitor indomethacin resulted in marked reduction of the water and sodium excretion induced by furosemide. It also blunted renal vasoconstriction and renin release by furosemide, but the glomerular filtration rate was not affected. Pretreatment with aprotinin, a kallikrein inhibitor, failed to affect the renal response to furosemide. The results indicate that the renal prostaglandin system, but not the kallikrein-kinin system, participates in the effect of furosemide on renal functions mainly through electrolyte transport inhibition in the renal tubule.

This study systematically evaluates the effect of changes in the acid-base composition of the incubation media on the electrogenic H+ and HCO3- secretion (voltage clamp method and serosal ouabain) in the isolated turtle urinary bladder. Since the various cell types would change their acidity in a similar direction but to a variable degree, measured mean cell pH values (5,5-dimethyl-2,3-oxazolidinedione method) were used for an overall assessment of the changes in the acid-base status of the acid-transporting cells. Although addition of exogenous CO2 (0.7-3%) increased H+ secretion (JH+) 2- to 4-fold from a CO2-free control period, a further increase in the percent of CO2 did not enhance JH+ demonstrating a permissive but not a stimulatory role of CO2. Cyclic AMP plus 3-isobutyl-1-methylxanthine-induced electrogenic HCO3 secretion (JHCO3-) remained unaltered at 10% CO2 from a 5% CO2 control period. Cell acidosis resulting from either alterations in the PCO2/HCO3- levels or from NH4Cl in the bathing solution did not enhance JH+; by contrast maximal levels of acidification were found at cell pH values of about 7.40 and comparable effects on JH+ were found with a variety of PCO2/HCO3- combinations that led to a similar intracellular acidity.

The purpose of the present review is to describe the use of carbonic anhydrase inhibitors in clinical medicine and renal physiology. We first describe the localization of carbonic anhydrase within the kidney and then discuss evidence for its role in renal acidification and NaCl absorption. This is then followed by a description of clinical uses for carbonic anhydrase inhibitors. Many of the uses and effects of carbonic anhydrase inhibitors can be predicted from an understanding of renal physiology and the role of carbonic anhydrase. The limited potency of carbonic anhydrase inhibitors correlates well with the large magnitude of carbonic anhydrase-independent bicarbonate absorption. While theories for carbonic anhydrase-independent bicarbonate absorption are presented, the exact mechanisms remain unresolved.