Role of nitric oxide in the regulation of blood flow in the rat submandibular gland during carotid artery occlusion.

The possible involvement of nitric oxide in the preservation of blood flow to the rat submandibular gland after uni- or bilateral occlusion of the common carotid was studied. Glandular blood flow and mean blood pressure were monitored before, during and after carotid occlusion in the presence and absence of the nitric oxide synthase inhibitor N(omega)-nitro-L-arginine-methyl-ester (L-NAME). To calculate vascular resistance, the local perfusion pressure distal to the point of occlusion was also measured. In normal rats, uni- or bilateral carotid occlusion resulted in an immediate decrease in ipsilateral glandular blood flow. After the cessation of carotid occlusion, hyperaemia was observed in the submandibular gland. Both local perfusion pressure and vascular resistance decreased during carotid occlusion. In the group pretreated with L-NAME, trends in blood-flow responses to uni- or bilateral occlusion were identical to those registered in the control groups, though the magnitude of the alterations was significantly less. The well-maintained glandular blood flow was due to functioning vascular anastomoses and compensating dilatation of glandular blood vessels. Nitric oxide had only a restrained effect on this compensatory mechanism.

Nitric oxide synthase inhibitor L-NAME has no effect on 86Rb accumulation in rat renal cortical slices.

UNLABELLED: The aim of present study was to investigate the effect of the nitric oxide synthase inhibitor L-NAME on the 86Rb uptake in rat renal cortical slices. Rats were divided into three groups: 1. CONTROL. 2. Acute: L-NAME (10 mg/kg i.v.) as a bolus 15 min before the excision of the kidneys. 3. Sub-chronic: L-NAME (10 mg/kg/day) per os for 4 days. Renal cortical slices were incubated for 10, 20, 30, 60, 90, 180 seconds in Krebs-Ringer solution containing 50 kBq 86Rb/100 ml (T = 37 degrees C, PO2 approximately 159 mm Hg). 56Rb accumulation (S/M) was calculated as the ratio of the radioactivity of the cortical slices (S) and the radioactivity of the incubating medium (M). The S/M ratio can be described as a function of time by the following equations. CONTROL: y = 0.265 ln(x) - 0.220, r(xy) = 0.886; acute L-NAME: y = 0.224 ln(x) - 0.171, r(xy) = 0.921; sub-chronic L-NAME: y = 0.331 ln(x) - 0.496, r(xy) = 0.942. (y = S/M, x = t). p < 0.001 in all of the groups, but there is no difference between the groups. In conclusion, L-NAME administered in vivo failed to influence the in vitro 86Rb accumulation in rat renal cortical slices.

Effect of indomethacin on extracellular space, sodium compartment and sodium excretion in saline loaded rats.

The effects of indomethacin, an inhibitor of prostaglandin synthesis, were studied on the sodium and fluid balance of rats kept on a normal diet and physiologic saline for two weeks. Under the effect of indomethacin the inulin compartment (extracellular space) and Na(24)-compartment expanded from 20.5 plus or minus 4.1 to 25.2 plus or minus 5.1 ml per 100 g, (p.less than 0.001); and from 31.9 plus or minus 2.8 to 37.0 plus or minus 5.6 ml per 100 g, (p less than 0.001), respectively, and the exchanged amount of Na+ increased from 4.33 plus or minus 0.5 to 5.01 plus or minus 1.03 mEq per 100 g, (p less than 0.02). On the other hand, fluid and Na+ uptake and excretion were unaffected. Haematocrit and plasma protein levels decreased (from 42.5 plus or minus 2.98 to 38.6 plus or minus 5.2%, p less than 0.01; and from 5.41 plus or minus 0.67 to 5.01 plus or minus 0.47 g/dl; p less than 0.05, respectively). The experimental findings supported the assumption that (a) under conditions of saline loading the prostaglandins might play a role in the mechanism of natriuresis and their absence might lead to sodium and water retention. (b) The indomethacin induced transient reduction in salt and water excretion could be restored by the combined effect of volume regulating reflex mechanism and physicochemical factors (haemodilution).

Comparative study of the effects of indomethacin and sodium salicylate on the renal circulation.

Indomethacin and salicylates are considered to be specific inhibitors of prostaglandin (PG) synthesis. If their mechanism of actin is common then similar effects would be expected in organs capable of PG production. In the present investigation the effects on renal and intrarenal haemodynamics by indomethacin and Na-salicylate were studied and compared in anaesthetized (nembutal) dogs using SAPIRSTEIN's technique. Indomethacin (4 mg per kg) raised blood pressure while cardiac output remained unaffected. Sodium salicylate (200 mg per kg) also increased blood pressure, however, this was associated with increased cardiac output. Renal blood flow was depressed by indomethacin, whereas it was not influenced by Na-salicylate (RBFcontr. = 411 +/- 97; RBFindo. = 292 +/- 53, p less than 0.01; RBFNa-salic. = 468 +/- 110 ml per min per 100 g). Renal resistance was augmented after indomethacin and unaltered by Na-salicylate (Rcontr. = 1.96 +/- 0.43; Rindo. = 3.03 +/- 0.97, p less than 0.001; RNa-salic. = 1.91 +/- 0.49). Indomethacin provoked an intrarenal blood flow redistribution, while no such effect was seen by Na-salicylate. Salt and water excretion was markedly suppressed by indomethacin, whereas Na-salicylate exhibited diuretic and natriuretic actions. It is concluded that the two agents exert their actions on renal haemodynamics and salt and water excretion by different mechanisms. The differential responses might be accounted for by the finding that Na-salicylate fails to inhibit renal PG-production.

Sodium and water transport in frog skin: effect of indomethacin.

UNLABELLED: The transepithelial transport of sodium, rubidium and water was studied in the frog skin in the presence of the cyclic endoperoxidase inhibitor indomethacin. Sodium transport was studied by measuring short circuit current and by 24Na radioactive isotope method; water transport was examined using the frog skin sac technique. Indomethacin produced the following changes. 1. The transepithelial potential difference and the intensity of short circuit current were decreased, while the resistance and conductance of the skin remained unaltered. 2. Passive transepithelial sodium transport from the inner to the outer side was enhanced. 3. Neither osmotic water transport nor passive rubidium transport were changed. CONCLUSIONS: a) Indomethacin causes a selective increase of sodium permeability in the frog skin; b) The present results are in agreement with the view that the indomethacin may influence the rate of sodium transport in some tissues.

In vitro and in vivo analysis of para-aminohippuric acid (PAH) transport: effect of indomethacin.

Effect of the prostaglandin synthesis inhibitor, indomethacin (indo) were studied on renal PAH transport (a) in renal cortical slices in vitro and (b) in anaesthetized dogs with various levels of plasma PAH concentrations (b1:PPAH less than 3 mg/dl and b2:PPAH V greater than 20 mg/dl] in vivo. It was found that: (a) indomethacin in concentrations of 0.4 and 4.0 micrograms/ml failed to influence PAH accumulation (S/M) and K or Na contents in renal cortical slices, whereas in a concentration of 40 micrograms/ml it potently decreased PAH accumulation (S/Mcontrol: 4.62 +/- 0.76, S/Mindo: 2.38 +/- 0.41; p less than 0.001). The oxygen uptake by tissue slices remained unaltered in the presence of indomethacin. (b1) Indomethacin in a dose of 4 mg/kg produced a pronounced antidiuresis and antinatriuresis with no change in GFR. PAH secretion was slightly reduced (TPAH control: 3.97 +/- 1.21; TPAH indo: 3.21 +/- 1.55 mg/min/100 g; p less than 0.01). (b2) Indomethacin appreciably decreased the secretory maximum of tubules (TmPAH control: 10.0 +/- 4.39; TmPAH indo: 4.95 +/-3.83 mg/min/100 g; p less than 0.001). Based on these results it is concluded that indomethacin, even when applied in the usual concentration, might partially block certain enzymes in the kidney.

Effect of indomethacin on intrarenal circulation and sodium and water excretion in anaesthetised rats with or without acute volume expansion.

Effects of the prostaglandin synthesis inhibitor indomethacin (4 mg/kg) were studied on the intrarenal circulation of anaesthetised (pentothal 50 mg/kg i.p.) rats in normovolemia or subjected to acute extracellular volume expansion (intravenous infusion of 0.9% NaCl at a dose of 50 ml/kg) using Sapirstein's 86Rb indicator dilution technique. Circulatory parameters were determined one hour after indomethacin treatment. The following conclusions were drawn: 1. In normovolemic rats the renal, cortical and medullary blood flow remained unaltered. No changes occurred in regional vascular resistances of the kidney or in the distribution pattern of intrarenal blood flow. Water output was moderately reduced while sodium excretion remained unaffected. 2. In rats subjected to acute extracellular volume expansion renal cortical blood flow was slightly augmented, medullary perfusion rate declined; the intrarenal blood flow distribution was shifted towards the cortex. The vascular resistance in the cortex did not change whereas that in the medulla was slightly augmented. Under these conditions indomethacin did not influence salt and water excretion. Our results provide further evidence that unlike in anaesthetised dog, in the anaesthetised rat endogenous prostaglandins probably do not play a decisive role in the control of renal blood flow, intrarenal circulation and salt and water excretion.

Comparative haemodynamic studies of resting and active skeletal muscle in anaesthetised rats: role of nitric oxide.

Our previous studies have indicated that nitric oxide takes part in the basal regulation of vascular tone in skeletal muscle. The purpose of this study was to investigate whether nitric oxide has a role in the active hyperaemic response of a working muscle in a resting subject. Haemodynamic effects of nitric oxide synthase (NOS) inhibition (L-NAME, 10 mg/kg/30 min i.v. infusion) were determined simultaneously in the resting m. quadriceps femoris and in the working (breathing) m. rectus abdominis in anaesthetised rats (86Rb accumulation technique). L-NAME increased blood pressure and total peripheral resistance (TPR) while it decreased cardiac output. Blood flow (BF) decreased and vascular resistance (VR) increased both in resting (BF: 8.91+/-1.97-->5.92+/-2.59 ml/min/100 g, p<0.05: VR: 106+/-29.9-->212+/-113 R, p<0.01) and working (BF: 17.0+/-4.78-->6.93+/-2.15 ml/min/100 g, p<0.001; VR: 57.0+/-18.5-->160+/-56.7 R, p<0.01) muscle following NOS inhibition, but the percentile change of BF was higher in the working muscle (59%) than in the resting one (34%, p<0.001). There was a positive correlation between the cardiac output and the blood flow of the resting muscle with or without L-NAME administration, but blood flow of the working muscle failed to have any correlation with the cardiac output in control animals. However, L-NAME administration decreased both the cardiac output and the blood flow and similarly to the resting muscle a positive correlation was found. In conclusion, the haemodynamic effects of NOS inhibition are higher in working muscle than in the resting one: the nitric oxide may have important role in vasodilatation during muscle activity.

Cardiac output distribution and intrarenal haemodynamics: role of thromboxanes.

The effects of imidazole, an inhibitor of thromboxane synthesis, were studied on the distribution of cardiac output and on the intrarenal haemodynamics in anaesthetized, furthermore on the salt and water excretion in conscious rats. Imidazole treatment (10 mg/100 g b.m., intraperitoneally, twice a day for two days) failed to influence the arterial blood pressure, the cardiac output and its distribution in organs investigated (heart, muscle, lung [bronchial fraction], skin, liver, spleen, small intestine, adrenal gland and kidneys). The medullary blood flow increased, while cortical blood flow remained unchanged, but the intrarenal percentile blood flow shifted towards the medulla. Imidazole elevated the water turnover in the animals, but no change in sodium and potassium excretion occurred. It is supposed that thromboxanes may affect the renal medullary vascular tone without altering the vascular smooth muscle activity in other organs.

Intrarenal distribution of renal blood flow after acute and chronic administration of nitric oxide-synthase inhibitor.

UNLABELLED: The effects of acute and chronic inhibition of endothelium derived relaxing factor (EDRF/NO) synthesis were investigated on the intrarenal blood flow in anaesthetized rats. N omega-nitro-L-arginine methyl ester (L-NAME, 10 mg/kg) was used for inhibition of NO-synthase. In acute experiments L-NAME was infused, while in chronic experiments L-NAME (4-day pretreatment) was dissolved in the drinking water. Blood flow was measured by 86-Rubidium accumulation method. Renal blood flow decreased markedly after both acute and chronic L-NAME treatment. (Acute: RBF-control: 679 +/- 122, RBF-L-NAME: 333 +/- 65 ml/min/100 g, p < 0.01; Chronic: RBF-control: 527 +/- 133, RBF-L-NAME: 315 +/- 75 ml/min/100 g, p < 0.01). The consequences of the NO-synthase blockade are different in the cortical and medullary vessels. The increase in the vascular resistance in the medulla (in acute experiments 228%, R-control: 2.76 +/- 0.76, R-L-NAME: 9.08 +/- 4.36 R, p < 0.01; in chronic experiments 113%, R-control: 3.89 +/- 1.20, R-NAME: 8.31 +/- 3.75 R, p < 0.01) is appreciably greater than in the cortex (acute blockade: 112%, R-control: 1.12 +/- 0.29, R-L-NAME: 2.38 +/- 0.47 R, p < 0.01; chronic blockade: 62%, R-control: 1.61 +/- 1.03, R-L-NAME: 2.61 +/- 0.61 R, p < 0.01). The percentile distribution of intrarenal blood flow shifts from the medulla toward the cortex following acute NO-synthase blockade (MBF-control: 16.8 +/- 1.11%; MBF-NAME: 12.3 +/- 2.66%, p < 0.01). The proportion of cortical and medullary blood flow remains unaltered after chronic NO-synthase inhibition. CONCLUSION: The nitric oxide plays an important role in determining the renal, cortical and medullary blood flow. The effect of EDRF in influencing the vascular resistance is more pronounced in the medulla than in the cortex.

Nitric oxide synthase inhibition increases vascular resistance in sodium and water loaded rats.

The aim of this study was to investigate whether nitric oxide might be involved in the adaptation of the cardiovascular system in sodium and water loaded organisms. The effects of a semi-chronic (4 day) inhibition of nitric oxide production were studied in normovolemic and per os sodium and water loaded rats. Nitric oxide synthase was inhibited by L-NAME (10 mg/kg in normovolemic and 14 mg/kg in sodium loaded rats) dissolved in the drinking solution. Blood pressure, cardiac output (Stewart-Hamilton's principle) and its regional fractions (Sapirstein's technique using 86Rb isotope as indicator), total peripheral resistance and regional vascular resistances were determined on the 5th day in sodium pentobarbital anaesthesia. The increase in blood pressure following L-NAME pretreatment in both groups was similar, but the elevation of total peripheral resistance was 106% in normovolemic and only 30% in sodium loaded animals. The cardiac output decreased by 44% in normovolemic and 14% in sodium loaded groups after nitric oxide synthase inhibition. The organ vascular resistances increased and organ blood flows decreased after L-NAME administration. These changes were less pronounced in sodium and water load, especially those in the skeletal muscle and intestine. Nitric oxide-induced changes in vascular resistance are more pronounced in normovolemia than in sodium load; sodium load might influence the nitric oxide production. The share of nitric oxide in the setting of vascular tone is different in the various organs.

Different effects of naproxen on the organ blood flows in normo- and hypervolemic anaesthetized rats.

The effects of naproxen, an inhibitor of the enzyme cyclooxigenase (10 mg/kg i.v.) on the distribution of the cardiac output (CO) and on the intrarenal hemodynamics were investigated in normovolemic (free salt and water uptake till the beginning of experiment) and hypervolemic (with i.v. infusion of 50 ml 0.9% NaCl solution/kg/10 min) narcotized rats. The cardiac output was measured on the basis of he Stewart-Hamilton principle, the blood flow of the organs by the Sapirstein method. 86Rb was used as indicator. In hypervolemia, the blood pressure is the same, the cardiac output is higher (CO-normovolemia: 23.1 +/- 7.04, CO-hypervolemia: 29.0 +/- 6.43 ml/min/100 g; p < 0.05) the total peripheral resistance (TPR) is lower (TPR-normovolemia: 40.0 +/- 9.39 R, TPR-hypervolemia: 31.2 +/- 8.34 R, p < 0.05) than in normovolemic animals. In hypervolemia the vascular resistance of the investigated organs (heart, lungs, kidney, skin, muscle, liver, spleen, intestine) is also lower and the intrarenal blood flow shifts toward the medulla. One hour following the naproxen administration a) in normovolemia joining to a slightly decreased cardiac output and increased TPR, the vascular resistance of the skin (R-control: 85.1 +/- 32.7, R-naproxen: 161 +/- 57.4; p < 0.001) and of the skeletal muscle (R-control: 114 +/- 35.1, R-naproxen: 190 +/- 81.9; p < 0.01) increases. The blood flow of the other organs and the intrarenal hemodynamics does not change under the effect of naproxen. b) in hypervolemia the general circulatory parameters (blood pressure, cardiac output, TPR) and the parameters of the organ circulation and intrarenal hemodynamics remain unchanged. The results suggest that in rats the prostanoid compounds (PGE2, PGI2, TXA2) a) can modify the blood flow of the skin and muscle in normovolemic animals, but they do not have any role in determining the blood flow of the other organs or the intrarenal distribution of blood flow. b) in hypervolemia they play no role in determining organ-, or intrarenal blood flow. The consequences of cyclooxygenaze enzyme inhibition--at least in the case of the organ blood flow--depend on the magnitude of sodium and water load in the organism.

Changes of organ blood flow and cardiac output after imidazole administration.

Effects of imidazole, an inhibitor of thromboxane synthesis (10 mg/kg bw., iv.) on the distribution of cardiac output and intrarenal hemodynamics were investigated in normovolemic (free water and salt uptake before the experiment) narcotized rats. The cardiac output was measured on the basis of the Stewart-Hamilton principle, the blood flow of the organs by the Sapirstein method. 86Rb was used as indicator. One hour following the imidazole administration while mean arterial blood pressure remained constant a slight drop in the cardiac output (CO) was observed (CO-control: 24.1 +/- 4.77; CO-imidazole: 20.6 +/- 2.40 ml/min/100 g; p < 0.05) and total peripheral resistance increased (TPR-control: 42.3 +/- 9.27; TPR-imidazole: 48.3 +/- 7.05 R; p < 0.05). The vascular resistance in the heart, lungs (bronchial fraction), liver, spleen, intestine and adrenal glands remained unchanged. The blood flow of the skin and skeletal muscle decreased moderately, their vascular resistance increased following imidazole treatment. Inhibition of the thromboxane synthesis did not influence the renal and intrarenal (cortex and medulla) circulation, the percentile distribution of the intrarenal blood flow remained unchanged. The results suggest that TXA2 does not play a definite role in maintaining the a) vascular tone (blood flow) of different organs b) intrarenal hemodynamics (salt and water excretion) in normovolemic rats.

Effects of indomethacin and naproxen on renal p-amino-hippurate (PAH) excretion in rats during postnatal development.

Effects of the cyclooxygenase inhibitors indomethacin and naproxen on renal PAH excretion were studied in volume-expanded and sodium-loaded, conscious rats of different ages. Indomethacin and naproxen reduce renal PAH excretion in 5- and 10-day-old rats but not in rats of older ages. Findings can be explained by a decrease in glomerular filtration rate. In addition, a competitive inhibition of PAH transport by the organic acids indomethacin and naproxen must be mentioned. Until now it is not known whether or not there is a direct or indirect influence of prostaglandins on processes involved in tubular PAH transport.

Effect of neonatal sympathectomy by 6-hydroxydopamine on renal hemodynamic parameters in adult rats.

Newborn rats were sympathectomized with 6-hydroxydopamine (6-OHDA) (10 mg/100 g b.w., once daily on the first 4 postnatal days). Hemodynamic parameters were determined at the 55th d of life. In comparison to non-sympathectomized control rats the blood pressure and total peripheral resistance of 6-OHDA treated animals were significantly diminished whereas the cardiac output was enhanced. In sympathectomized rats the resistance values of the whole kidney as well as of the cortex and outer medulla were lower than in control animals. No redistribution of renal blood flow was detectable. The results show a long lasting effect of neonatal denervation by 6-OHDA at least up to the 55th d of life.

Blood flow of the right and left submandibular gland during unilateral carotid artery occlusion in rat: role of nitric oxide.

UNLABELLED: The aim of the present study was to investigate the effect of unilateral carotid artery occlusion on the blood flow of submandibular gland in anesthetized rats and identify the role of nitric oxide (NO) in blood flow changes after the artery occlusion. L-NAME (N omega-nitro-L-arginine-methyl-ester; 10 mg/kg/day, per os) dissolved in tap water was used to block nitric oxide synthase. Glandular blood flow was measured using Sapirstein's indicator (86Rb) distribution technique. In the control animals the blood flow of left (ligated side) submandibular gland was lower than in the right (unligated side) one (right: 76.4+/-15.4 ml/min/100 g, 64.1+/-13.4 ml/min/100 g, p<0.01). The blood flow of submandibular glands decreased in NOS blocked group versus control. The vascular resistance after L-NAME treatment was elevated (control: 11+/-2.3 R/kg, L-NAME: 17.5+/-4.1 R/kg, p<0.001). In L-NAME group the difference between blood flow value of the left and right submandibular gland was significantly lower than in the control group (control: -16%, NAME: -8%, p<0.01). CONCLUSION: The maintenance of the blood flow in the left submandibular gland during ligation of the left common carotid artery could be due to the good vascular anastomotic system at these regions and adaptation of the submandibular vessels to the decreased perfusion pressure. Nitric oxide may have a role in the regulation of blood flow tinder this condition.

Comparison of the effects on inhibition of cyclooxygenase and thromboxane synthetase on renal excretion and haemodynamics in rats of different ages.

Effects of the cyclooxygenase inhibitors indomethacin, naproxen and the thromboxane synthetase inhibitor imidazole on renal sodium water and p-aminohippurate excretion were investigated in sodium loaded conscious rats of different ages. Renal and intrarenal blood flow were studied in anaesthetized adult rats. Indomethacin and naproxen reduced PAH excretion in 5- and 10-day-old rats but not in rats of older ages. Imidazole failed to influence PAH-excretion in young animals. The excretion of PAH was decreased in adult rats at 10 and 60 min following imidazole administration, but not after longer time interval (120 min). Following indomethacin and naproxen administration urine output was decreased in 5-, 10- and 15-day-old rats, but not in rats of older ages. Effects of imidazole on electrolyte excretion can be demonstrated in adult rats only. Cardiac output was not altered by the three drugs. Blood pressure was elevated after indomethacin, but remained unchanged after naproxen and imidazole treatment. Renal and cortical blood flow remained unaltered and no redistribution was seen in intrarenal blood flow after indomethacin, naproxen and imidazole administration. The experimental data suggest that prostaglandins and thromboxanes are involved in the regulation of kidney function, but prostaglandins in the rat--in contrast to the dog--do not seem to play a major role in the regulation of renal vascular tone in adult animals.

Blood flow of the submandibular gland in sodium-depleted and -loaded rats: effect of nitric oxide synthase inhibition.

The present investigations were designed to study the hemodynamic effects of different sodium diets in the submandibular gland of rats with or without nitric oxide (NO) synthesis inhibition. Experimental animals were kept on: (1) standard chow and tap water ad libitum (normal group, N), or (2) wheat and distilled water ad libitum for 4 weeks (sodium-depleted animals, SD), or (3) standard chow and saline ad libitum for 4 weeks (sodium-loaded animals, SL). NO synthase was inhibited by N omega-nitro-L-arginine-methyl-ester (L-NAME, 10 mg/kg per day) in the last week. The rats were anesthetized, and blood pressure, cardiac output (Stewart-Hamilton's principle) and blood flow (BF) of the submandibular gland (Sapirstein's technique) were determined. High sodium intake resulted in a 47% increase of glandular BF as compared to BF measured in the control group. In all groups L-NAME decreased BF (ml/min per 100 g gland) as compared to those of rats with no L-NAME treatment (N: 76.4 +/- 15.4 vs. 56.0 +/- 11.6, P < 0.05; SD: 71.0 +/- 17.7 vs. 56.2 +/- 15.1, n.s.; SL: 112 +/- 29.4 vs. 66.9 +/- 18.4, P < 0.001), whereas the vascular resistance (VR, mm Hg x ml-1 x s x kg-1) increased (N: 11.0 +/- 2.3 vs. 17.5 +/- 4.1, P < 0.001; SD: 11.0 +/- 2.7 vs. 17.0 +/- 4.2, P < 0.01; SL: 8.5 +/- 2.4 vs. 14.9 +/- 4.6, P < 0.001). The increase in VR after L-NAME treatment was 64% in normal, 55% in sodium-depleted and 75% in sodium-loaded rats. Our results suggest that NO takes part in the regulation of vascular resistance and BF in the submandibular gland. Sodium load itself increases BF of the submandibular gland and this phenomenon may partly be mediated by NO.

Effect of nitric oxide synthase inhibition on renal circulation and excretory function in anaesthetized rats.

The effects of nitric oxide synthase (NOS) inhibition (effected using L-NAME, 14 mg (kg body mass (BM))(-1), administered intravenously) on systemic and renal circulation and renal excretory function has been investigated in anaesthetized Wistar rats subjected to one of two different degrees of isotonic extracellular (EC) volume expansion (40 and 60 ml x kg(-1) (240 min)(-1)). The administration of L-NAME resulted in an increase in mean arterial blood pressure and total peripheral vascular resistance (TPR), and a significant reduction in cardiac output (CO) and the kidney fraction of CO in both experimental groups. The total renal blood flow (RBF) dropped from 557 + 43.4 to 149 +/- 13.1 ml x min(-1) (100 g BM)(-1) and from 592 +/- 45.9 to 191 +/- 16.3 ml x min(-1) (100 g BM)(-1) in the 40 and 60 ml x kg(-1) (240 min)(-1) experimental volume expansion groups, respectively. A redistribution of the intrarenal circulation from the medulla of the kidney toward the cortex may have occurred. The NOS inhibition induced a significant decrease in the glomerular filtration rate (GFR; from 1.18 +/- 0.10 to 0.53 +/- 0.08 ml x min(-1) (100 g BM)(-1) and from 1.26 +/- 0.07 to 0.73 +/- 0.08 ml x min(-1) (100 g BM)(-1) in the 40 and 60 ml x kg(-1) (240 min)(-1) experimental volume expansion groups, respectively), and the filtration fraction increased. The urine excretion dropped in parallel with the GFR, while the reduction in sodium and potassium excretion was more marked than that of the GFR, raising the possibility of a direct effect on the kidney tubules. The difference in EC volume expansion (the calculated increases in the EC volume in the last 90 min were 1.30 and 5.44% in the two time control groups and 3.66 and 7.45% in the two L-NAME-treated groups) did not induce any significant modification of the L-NAME effect.

Intrarenal distribution of blood flow in sodium depleted and sodium loaded rats: role of nitric oxide.

The renal hemodynamic effects of nitric oxide synthase (NOS) inhibition and dietary salt were studied in rats. L-NAME (0.1 mg/ml in the drinking fluid, about 12 mg/kg/day) was given for 4 days to rats receiving low (sodium depletion, SD), normal (N) or high (sodium load, SL) NaCl diet. Intrarenal hemodynamics was studied in anaesthesia. NOS inhibition decreased renal blood flow and increased renal vascular resistance in each group. Cortical and outer medullary but not inner medullary blood flow increased in direct ratio to the sodium intake. NOS inhibition decreased the blood flow and increased the vascular resistance in all layers of the kidney in SD, N, and SL rats as well. In SD and N, but not in SL rats L-NAME induced vasoconstriction was higher in the outer (OM) and inner medulla (IM) than in the cortex (C) [SD: DeltaCVR 43%, DeltaOMVR 54%, DeltaIMVR 84%; N: DeltaCVR 54%, DeltaOMVR 96%, DeltaIMVR 106%; SL: DeltaCVR 50%, DeltaOMVR 64%, DeltaIMVR 35%]; in normal rats blood flow shifts from the medulla toward the cortex. In conclusion, nitric oxide may have a role in the regulation of renal vascular tone not only in the case of regular sodium uptake but in the sodium depleted or loaded organism as well. However, nitric oxide has no role in the dietary salt evoked vascular adaptation in the kidney.