The effects of Trichinella spiralis infection on renal function in rats.

Trichinella spiralis infection was induced in rats by oral feeding of infective larvae. Four weeks later, renal function, including renal plasma flow (RPF), glomerular filtration rate (GFR), excretion rate of protein, sodium and potassium were determined using clearance technics. There were no significant changes in these parameters. However, plasma urea nitrogen was significantly higher in the infected group, suggesting that either an impaired regulation of renal tubular urea transport or an increased skeletal muscle breakdown is likely.

Effects of angiotensin II receptor blockade on proximal fluid uptake in the rat kidney.

Angiotensin II has a well described dose-dependent biphasic action on proximal tubule fluid uptake, although the concentration and effect of endogenous luminal angiotensin II remain controversial. Shrinking split-droplet micropuncture was used to examine the fluid uptake in response to the luminal application of three AT1 antagonists (losartan, EXP3174, candesartan). Addition of losartan at 10(-8) M decreased fluid uptake rate (Jva) by 17.5+/-2.2% (P<0.05). Luminal addition of EXP3174 at concentrations between 10(-9)-10(-5) M caused a dose-dependent decrease in fluid uptake, with a maximum decrease of 41.0+/-9.5% (P<0.01) at 10(-6) M. Candesartan also decreased fluid uptake, by 21.9+/-4.9% (P<0.05) at 10(-8) M and 23.6+/-5.5% (P<0.05) at 10(-5) M. All three antagonists at a low concentration (10(-8) M) decreased fluid uptake. EXP3174 and candesartan at a higher concentration (10(-5) M) also decreased fluid uptake in contrast to the previously reported effect of losartan. We conclude that the endogenous concentration of antiotensin II in the proximal luminal fluid is low and exerts a stimulatory effect on fluid absorption. Losartan at concentrations greater than 10(-6) M may have a non-selective action on fluid uptake.

Inhibition of proximal tubular fluid absorption by nitric oxide and atrial natriuretic peptide in rat kidney.

Atrial natriuretic factor (ANF) and nitric oxide (NO) stimulate production of guanosine 3',5'-cyclic monophosphate (cGMP) and are natriuretic. Split-drop micropuncture was performed on anesthetized rats to determine the effects of ANF and the NO donor sodium nitroprusside (SNP) on proximal tubular fluid absorption rate (Jva). Compared with control solutions, SNP (10(-4) M) decreased Jva by 23% when administered luminally and by 35% when added to the peritubular perfusate. Stimulation of fluid uptake by luminal angiotensin II (ANG II; 10(-9) M) was abolished by SNP (10(-4) and 10(-6) M). In proximal tubule suspensions, ANF (10(-6) M) increased cGMP concentration to 143%, whereas SNP (10(-6), 10(-5), 10(-4), 10(-3) M) raised cGMP to 231, 594, 687, and 880%, respectively. S-nitroso-N-acetylpenicillamine (SNAP) also raised cGMP concentrations with similar dose-response relations. These studies demonstrate inhibition by luminal and peritubular NO of basal and ANG II-stimulated proximal fluid absorption in vivo. The ability of SNP to inhibit basal fluid uptake whereas ANF only affected ANG II-stimulated transport may be because of production of higher concentrations of cGMP by SNP.

Amylin stimulates proximal tubular sodium transport and cell proliferation in the rat kidney.

In autoradiographic studies in anesthetized rats, 125I-labeled amylin binding was associated with proximal convoluted tubules but not distal tubules, interstitium, or glomeruli in the renal cortex. Split-drop micropuncture experiments showed that perfusion of the peritubular capillaries with amylin (10(-9) M) stimulated proximal tubular fluid absorption by 28%. This effect was inhibited by luminal addition of ethylisopropylamiloride, indicating mediation by a brush-border Na+/H+ exchanger. Intravenous infusion of an amylin binding antagonist, AC-187, reduced proximal fluid reabsorption (22%) in anesthetized rats, indicating a role for endogenous amylin in salt homeostasis. In primary cultures of rat proximal tubule cells, amylin (10(-7) M) stimulated proliferation with a potency equal to epidermal growth factor. Peptide antagonists (AC-187, AC-413, and AC-512) of the amylin binding sites in the renal cortex blocked the mitogenic action of amylin. We conclude that amylin acts on renal proximal tubules to promote sodium and water reabsorption and cell proliferation. These novel actions may have implications for the development of hypertension for example in non-insulin-dependent diabetes mellitus and obesity in which hyperamylinemia has been observed.

Modulation by locally produced luminal angiotensin II of proximal tubular sodium reabsorption via an AT1 receptor.

The concentration of angiotensin II reported in proximal tubular fluid in anaesthetized rats is considerably higher than in plasma, indicating secretion of this peptide into the tubular lumen. Shrinking split-drop micropuncture was used to examine the effect of endogenous angiotensin on sodium and water absorption in the proximal convoluted tubule. Addition of losartan, a nonpeptide AT1 receptor blocker, to intratubular fluid increased fluid uptake by 15.7 +/- 3.9% (10(-5) M) and 24.7 +/- 9.4% (10(-4) M) whereas the AT2 inhibitor, PD123319 had no effect. We conclude that angiotensin II is secreted into proximal tubular fluid and, in the anaesthetized rat, is maintained at a concentration that inhibits sodium and water transport via AT1 receptors.

Regulation of renal tubular sodium transport by angiotensin II and atrial natriuretic factor.

1. The effects of angiotensin II (AngII) on water and electrolyte transport are biphasic and dose-dependent, such that low concentrations (10(-12) to 10(-9) mol/L) stimulate reabsorption and high concentrations (10(-7) to 10(-6) mol/L) inhibit reabsorption. Similar dose-response relationships have been obtained for luminal and peritubular addition of AngII. 2. The cellular responses to AngII are mediated via AT1 receptors coupled via G-regulatory proteins to several possible signal transduction pathways. These include the inhibition of adenylyl cyclase, activation of phospholipases A2, C or D and Ca2+ release in response to inositol-1,4,5,-triphosphate or following Ca2+ channel opening induced by the arachidonic acid metabolite 5,6,-epoxy-eicosatrienoic acid. In the brush border membrane, transduction of the AngII signal involves phospholipase A2, but does not require second messengers. 3. Angiotensin II affects transepithelial sodium transport by modulation of Na+/H+ exchange at the luminal membrane and Na+/HCO3 cotransport, Na+/K(+)-ATPase activity and K+ conductance at the basolateral membrane. 4. Atrial natriuretic factor (ANF) does not appear to affect proximal tubular sodium transport directly, but acts via specific receptors on the basolateral and brush border membranes to raise intracellular cGMP levels and inhibit AngII-stimulated transport. 5. It is concluded that there is a receptor-mediated action of ANF on proximal tubule reabsorption acting via elevation of cGMP to inhibit AngII-stimulated sodium transport. This effect is exerted by peptides delivered at both luminal and peritubular sides of the epithelium and provides a basis for the modulation by ANF of proximal glomerulotubular balance. The evidence reviewed supports the concept that in the proximal tubule, AngII and ANF act antagonistically in their roles as regulators of extracellular fluid volume.

Regulation of renal tubular sodium transport by angiotensin II and atrial natriuretic factor.

1. The effects of angiotensin II (AngII) on water and electrolyte transport are biphasic and dose-dependent, such that low concentrations (10(-12) to 10(-9) mol/L) stimulate reabsorption and high concentrations (10(-7) to 10(-6) mol/L) inhibit reabsorption. Similar dose-response relationships have been obtained for luminal and peritubular addition of AngII. 2. The cellular responses to AngII are mediated via AT(1) receptors coupled via G-regulatory proteins to several possible signal transduction pathways. These include the inhibition of adenylyl cyclase, activation of phospholipases A(2), C or D and Ca(2+) release in response to inositol-1,4,5,-triphosphate or following Ca(2+) channel opening induced by the arachidonic acid metabolite 5,6,-epoxy-eicosatrienoic acid. In the brush border membrane, transduction of the AngII signal involves phospholipase A(2), but does not require second messengers. 3. Angiotensin II affects transepithelial sodium transport by modulation of Na(+) /H(+) exchange at the luminal membrane and Na(+)/HCO(3) cotransport, Na(+)/K(+)-ATPase activity and K(+) conductance at the basolateral membrane. 4. Atrial natriuretic factor (ANF) does not appear to affect proximal tubular sodium transport directly, but acts via specific receptors on the basolateral and brush border membranes to raise intracellular cGMP levels and inhibit AngII-stimulated transport. 5. It is concluded that there is a receptor-mediated action of ANF on proximal tubule reabsorption acting via elevation of cGMP to inhibit AngII-stimulated sodium transport. This effect is exerted by peptides delivered at both luminal and peritubular sides of the epithelium and provides a basis for the modulation by ANF of proximal glomerulotubular balance. The evidence reviewed supports the concept that in the proximal tubule, AngII and ANF act antagonistically in their roles as regulators of extracellular fluid volume.