Papillary Plasma Flow Research Articles

Hypertension from carotid occlusion decreases renal papillary plasma flow, hypotension from hemorrhage increases it, an autoregulatory paradox.

Renal papillary plasma flow was tested during acute increases and decreases of perfusion pressure using the 125I-labelled albumin technique. Increases of pressure were attained through ligation of carotid arteries; decreases of pressure through modest hemorrhage. In 12 control rats with blood pressure of 144 mmHg, the papillary plasma flow averaged 21.5 ml per 100 g papilla per min. In 12 rats after ligation of carotid arteries, blood pressure rose from 143 mmHg to 172, a 20% increase. The papillary plasma flow in these rats with acute hypertension averaged 17.9 ml per 100 g papilla per min, a 17% decrease (p < 0.025). In another 12 rats after bleeding 1% of body weight over a period of 10 min, blood pressure dropped from 146 mmHg to 104, a 29% decrease. The papillary plasma flow in these rats with acute hypotension averaged 26.0 ml per 100g papilla per min, a 21% increase (p < 0.025). The decrease in papillary plasma flow during acute hypertension strongly suggests an increased vascular resistance of the descending vasa recta, while the increase in papillary plasma flow during acute hypotension suggests that vasodilatation occurred in these vessels. This dilatation may be produced by the local release of prostaglandins or other vasoactive substances. Thus, the renal papilla appears to "overshoot" its autoregulation of plasma flow, with actual reduced flow during an acute blood pressure rise and increased flow during an acute blood pressure fall, an enigmatic over-compensation.

Reduced renal papillary plasma flow in non-ascitic cirrhotic rats.

1. The purpose of the present investigation was to determine whether an abnormality of the renal papillary circulation is present in a well-established model of cirrhosis without ascites (carbon tetrachloride/phenobarbital). 2. Compared with the control animals, cirrhotic rats showed a reduced diuretic (61.0 +/- 5.1 versus 18.0 +/- 2.5%) and natriuretic (67.8 +/- 8.3 versus 29.6 +/- 3.6%) response to a volume expansion (3% body weight infusion of 0.9% NaCl). The volume expansion-induced increase in renal interstitial hydrostatic pressure was also blunted in the cirrhotic rats (control 9.3 +/- 0.9 versus cirrhotic 6.1 +/- 1.0 mmHg) and there were no differences in mean arterial blood pressure, renal blood flow or glomerular filtration rate between control and cirrhotic animals. 3. Papillary plasma flow was determined by the 125I-albumin accumulation technique and expressed as ml min-1 100 g-1. In the basal state, papillary plasma flow was significantly lower in cirrhotic rats (59.1 +/- 4.4, n = 9) than in the control animals (81.8 +/- 6.9, n = 9). An isotonic saline expansion similar to the one described above significantly increased papillary plasma flow in control rats (108.4 +/- 9.1, n = 7) but did not change it in cirrhotic rats (60.2 +/- 4.9, n = 6). 4. Our results indicate the existence of a selective alteration in the renal papillary circulation in cirrhotic rats, both in the basal state and after a well-established vasodilatory stimulus.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of high-protein diet on renal concentration capacity in rabbits

In the present studies, we have found that New Zealand White rabbits kept on normal rabbit chow (16% protein, LP) are unable to raise fractional free water reabsorption [TCH2O divided by glomerular filtration rate (GFR)] as the fractional osmotic load (Cosm/GFR) is increased. Acute administration of urea (400 mosmol/l) or indomethacin (10 mg/kg iv bolus, followed by 0.25 mg/min infusion) corrects the defect. Moreover, rabbits kept for 2 wk on a 40% protein diet (HP) showed marked improvement in their renal concentration capacity. Balance studies showed that, in rabbits on HP, urine prostaglandin E2 (PGE2) excretion was lower while GFR, urine urea, and osmolar excretion were significantly higher than in rabbits in the LP group. Medullary tissue electrolytes in the HP vs. LP group were as follows: urea, 1,035 +/- 90 vs. 790 +/- 60 mmol.l-1 x g wet tissue wt-1; tissue Na+, 548 +/- 96 vs. 298 +/- 37 meq.l-1 x g wet wt-1; and K+, 201 +/- 43 vs. 99 +/- 16 meq.l-1 x g wet wt-1. Also, medullary slices from animals on HP had a lower PGE2 synthesis than those on LP when stimulated with angiotensin II (ANG II). Papillary plasma flow (PPF) measured by the accumulation of 125I-labeled albumin, after infusion of vasopressin, was 13.7 +/- 2.0 in the HP group and 22.7 +/- 3.4 ml.min-1 x 100 g-1 in the LP group. These findings suggest that lower PPF and higher urea and electrolyte content in the medullary interstitium of HP intake results from inability to produce medullary PGE2 even during ANG II or antidiuretic hormone (ADH) stimulation.(ABSTRACT TRUNCATED AT 250 WORDS)

Reversal of Na+ retention in chronic caval dogs by verapamil: contribution of medullary circulation.

The effects of verapamil on papillary plasma flow (PPF) and Na+ excretion were studied in anesthetized chronic caval dogs with low cardiac output and Na+ retention. Infusion of verapamil into the left renal artery (5 and 10 micrograms.kg-1.min-1) caused a dose-dependent ipsilateral increase in renal blood flow and Na+ excretion (from 10 +/- 2 to 171 +/- 32 and 225 +/- 35 mu eq/min, respectively). PPF in the left kidney was 26.6 +/- 4.4 and was significantly greater than that measured in the contralateral kidney (13.3 +/- 2.4 ml.min-1.100 g-1) (P < 0.01). The natriuresis occurred independent of changes in cardiac output and peripheral vascular resistance. In a separate group of caval dogs in which stimulation of the renin-angiotensin and adrenergic systems was intensified with a tighter caval constriction, verapamil failed to induce renal vasodilation or natriuresis and PPF was not altered. Despite the disparate hemodynamic responses, verapamil stimulated renal production of both renin and prostaglandin E2 in both groups of caval dogs. We conclude that the ability of verapamil to induce papillary vasodilation may contribute to the natriuresis seen in the caval dog, in which the site of Na+ retention includes the loop of Henle.

Failure of atrial natriuretic peptide to induce natriuresis in aortocaval fistula dogs.

Creation of an aortocaval fistula (ACF) in dogs induces salt and water retention, activation of the renin-angiotensin and adrenergic nervous systems and renal papillary ischemia associated with high levels of circulating atrial natriuretic peptide (ANP). The effects of intrarenal ANP (1.2 micrograms/min) infusion on systemic and renal hemodynamics, renal excretory function, renal output of renin and norepinephrine (NE) and papillary plasma flow (PPF) were studied in both normal and ACF dogs. ANP did not alter systemic hemodynamics in either group, but led to a significant increase in renal blood flow (RBF), glomerular filtration rate (GFR), urine flow rate (V), sodium excretion (UNaV) and fractional excretion of sodium (FENa), and a significant decrease in renal vascular resistance (RVR) and urine osmolality (UOsm) in normal dogs. GFR, RBF, RVR, V, UNaV, FENa and UOsm remained unchanged, however, in ACF dogs. In ACF dogs, both renal renin and NE output were significantly greater during baseline and remained significantly greater following ANP infusion, associated with a significantly lower PPF compared with normal dogs. These data suggest that ACF dogs are resistant to the renal effects of ANP, which can neither mitigate the hormonal mediators of sodium retention nor reverse the papillary ischemia observed in this model.

Physiological features of edematous dogs unresponsive to atrial natriuretic peptide

Sodium-retaining cirrhotic and chronic caval dogs with ascites show a heterogeneous natriuretic response to atrial natriuretic factor (ANF) infusions such that half will increase their urinary excretion of sodium and half will show no natriuretic response whatsoever. In these studies we have examined several physiological variables that might discriminate between these two experimental populations. We studied 22 caval dogs (11 natriuretic responders, 11 nonresponders) and 19 cirrhotic dogs (9 responders, 10 nonresponders). After an infusion of rat ANP-(1-28), 125 ng.kg-1.min-1, differences in glomerular filtration rate, blood pressure, or urinary excretion of guanosine 3',5'-cyclic monophosphate (cGMP) could not differentiate between the two types of dogs. When the left kidney of nonresponding dogs in both the caval and cirrhotic groups was either denervated or vasodilated with acetylcholine bromide (60-80 micrograms/min), the attenuation of the natriuretic response to ANF was not reversed. Papillary plasma flow (PPF) after ANF infusion was measured by a Lillienfield technique and averaged 36 +/- 4 ml.min-1.100 g-1 in normal dogs, 10.7 +/- 0.7 ml.min-1.100 g-1 in both responding and nonresponding caval dogs, and 48.3 +/- 1.1 ml.min-1.100 g-1 for each group of cirrhotic dogs. We conclude that differences in renal perfusion, PPF, cGMP generation, or the presence of intact renal nerves cannot explain the lack of a post-ANF natriuretic response in half of caval or cirrhotic dogs. Other physiological determinants must explain the heterogeneity of natriuretic response to ANF observed in edematous dogs.

Acute prostaglandin reduction with indomethacin and chronic prostaglandin reduction with an essential fatty acid deficient diet both decrease plasma flow to the renal papilla in the rat

Renal distribition of prostaglandin synthetase is mainly medullary, whereas the major degrading enzyme, prostaglandin dehydrogenase is primarily cortical. This suggests that prostaglandins (PG) released from the renal medulla could affect the medullary blood vessels. In two different experiments we studied the role of PG in the regulation of renal papillary plasma flow in the rat. First study: PG synthesis were stimulated in 34 adult Sprague-Dawley rats by bleeding from the femoral artery 1% of the body weight over a period of 10 minutes. Following this, indomethacin (a PG inhibitor, 10 mg/kg i.v.) was given slowly and then renal papillary plasma flow was measured 25 minutes after the end of infusion. In 17 indomethacin rats the renal papillary plasma flow averaged 18.8 ml/100 g/ minute, whereas it averaged 23.0 in 17 non-indomethacin rats given diluent, and 18% reduction (p < 0.25). Second study: Male Sprague-Dawley rats were made prostaglanding deficient by fasting rats for one week, followed by 10% dextrose fluid for one week and subsequent institution of an essential fatty acid (EFA) deficient diet for two weeks. With urinary PG excretion in prostaglandin deficient rats 28 ng/24 hours compared to 149 ng in control rats, they could be considered as prostaglandin deficient. When renal papillary plasma flow was measured, the 16 prostaglandin defecient rats had a 16% lower papillary plasma flow than 16 control rats, 21.6 vs 25.6 (p < .005). These results clearly demonstrate that PG inhibition in rats decreases plasma flow to the papilla, strongly suggesting that PG are vasodilators for the vessels supplying the renal papilla.

Regulation of papillary plasma flow by angiotensin II

We examined in anesthetized dogs the effects of left (L) intrarenal artery infusion of angiotensin II (AII) on renal hemodynamics, urinary concentration and Na excretion, and papillary plasma flow (PPF) (measured by the albumin accumulation technique) in both kidneys. Following AII infusion (0.5 ng/kg/min) into the L renal artery, urinary Na excretion decreased and osmolality increased slightly ipsilaterally, whereas Na excretion did not change significantly and osmolality decreased in the right (R) kidney. PPF was significantly lower in the L compared to the R kidney. When saline loading was superimposed on L intrarenal AII infusion, there was a blunted natriuretic response ipsilaterally with a significantly smaller decrease in urine osmolality compared with the R kidney. PPF increased significantly in the R, but not in the L kidney. Finally, AII blockade with saralasin prior to AII infusion and saline loading prevented the differences between the two kidneys, including PPF. In all groups GFR and renal blood flow did not differ between the two kidneys before or after AII. These data suggest that AII regulates regional blood flow in the medulla, and that the exogenously administered AII induces papillary ischemia, which serves to preserve medullary hypertonicity, preventing an increase in PPF during saline loading, and possibly contributing to the diminished natriuretic response.

Inner medullary hemodynamics in dogs with aortocaval fistula.

To investigate the role of medullary hemodynamics and vasoactive hormones in sodium retention in dogs with aortocaval fistula, we examined papillary plasma flow (PPF), solute content, and renal output of renin, norepinephrine, and prostaglandin E2 (PGE2) in anesthetized normal and fistula dogs. During hydropenia, cardiac output was elevated and systemic vascular resistance reduced in fistula dogs, accompanied by markedly increased renal output of renin, norepinephrine, and PGE2. In fistula dogs the blunted diuretic and natriuretic response to saline loading was not due to impaired myocardial contractility. During hydropenia and after saline loading, glomerular filtration rate (GFR) and renal blood flow were similar in normal and in fistula dogs; however, PPF was significantly lower in fistula dogs, accompanied by significantly greater papillary tissue osmolality and sodium content. These findings indicate that in fistula dogs enhanced medullary sodium reabsorption is associated with decreased PPF and stimulation of the renin-angiotensin and adrenergic nervous system. Furthermore, the reduced PPF obviates medullary solute washout during saline loading, and may contribute to the blunted diuretic and natriuretic response.

Additive effects of atrial natriuretic polypeptide and of renal vasodilating agents in the anesthetized dog

In order to examine the contribution of an increase in renal papillary plasma flow to the mechanism of natriuresis by atrial natriuretic polypeptide (ANP), we compared the natriuretic effects of ANP administered into the renal artery of the dog together with secretin or acetylcholine (ACh). At an equivalent renal vasodilating dose, ACh increased urinary excretion of sodium (U NaV) to 212 ± 36% of the control associated with a decrease in urine osmolality (62 ± 6%), whereas secretin did not change U NaV (113 ± 12%) or urine osmolality (101 ± 14%). This result was compatible with the view that ACh causes natriuresis mainly by increasing papillary plasma flow. Combined administration of ANP with secretin caused a marked increase in U NaV to 407 ± 55%, in association with a decrease in urine osmolality to 55 ± 9%, suggesting that ANP may cause natriuresis by a mechanism similar to that of ACh. Combined administration of ANP with ACh further increased U NaV to 323 ± 67% and decreased urine osmolality to 50 ± 6%. These observations suggest that ANP and ACh share common but not identical mechanisms of natriuretic action since ANP caused additional natriuresis during ACh infusion. These findings, however, do not necessarily exclude the possibility that ANP also inhibits renal sodium reabsorption by a direct action.

Effect of indomethacin on papillary solute concentration in the potassium-deficient rat.

Administration of indomethacin or meclofenamate to normal rats increases renal papillary solute concentration primarily by enhancing solute addition. A reduction in papillary solute concentration is characteristic of potassium deficiency. Of the multiple factors probably responsible for this reduction, several can be influenced by indomethacin or meclofenamate. The present study examined the effect of indomethacin on papillary solute concentration in the potassium-deficient rat. Indomethacin increased papillary solute concentration in normal but not potassium-deficient rats when studied in the conscious hydropenic state. Since indomethacin could increase papillary plasma flow in the potassium-deficient rat, potentially negating any enhancement of solute transport into the papilla, papillary plasma flow and papillary Cl concentration were determined in anesthetized surgically manipulated rats. Base-line papillary Cl concentrations were reduced in this setting. Indomethacin increased papillary plasma flow only in potassium-deficient rats but increased papillary Cl concentration equivalently in normal and potassium-deficient rats. The ability of indomethacin to increase papillary solute concentration in the potassium-deficient rat seemingly depends upon the experimental setting.

Role of renal papillae in the regulation of sodium excretion during acute elevation of renal perfusion pressure in the rat.

We studied the role of renal papillae in the mechanism of increased sodium excretion during acute increase in mean arterial pressure (MAP). Sodium excretion increased dramatically in normal rats after acute increase in MAP by epinephrine (E) infusion (0.4 micrograms/min/100g). Glomerular filtration rate (GFR), renal blood flow (RBF), and papillary plasma flow (PPF) remained unchanged after the E administration. To define the role of the medulla in the mechanism of pressure-induced natriuresis, experiments were performed in a group of rats 8 to 12 days after the development of papillary necrosis induced by bromoethylamine hydrobromide. Urinary sodium and fractional sodium excretions were 2.00 +/- 0.34 microEq/min and 2.37 +/- 0.53% (n = 7), respectively, in papillary necrosis rats infused with saline. Administration of E to papillary necrosis rats, however, failed to increase both urinary sodium (2.89 +/- 0.61 microEq/min) and fractional sodium (FENa, 2.82 +/- 0.63%, n = 6) excretions despite a marked increase in MAP (129 vs 150 mm Hg, p less than 0.01). The RBF increased slightly after E infusion (4.42 vs 3.24 ml/min/100 g, p less than 0.05), but the GFR was not different between the control (0.39 +/- 0.05 ml/min/100g, n = 7) and the E-treated rats (0.43 +/- 0.06, n = 6). Failure to increase sodium excretion during acute increase in MAP was not due to the decreased GFR, since control rats with bilateral partial nephrectomy were able to increase sodium excretion from 1.92 +/- 0.33 to 7.76 +/- 1.63 microEq/min (p less than 0.01) after E infusion. These findings, therefore, suggest that renal papillae play a major role in the mechanism of natriuresis during acute increase in MAP.

Inner medullary hemodynamics in chronic salt-depleted dogs.

The effects of chronic salt depletion on medullary hemodynamics remain unknown. In the present study, sodium excretion, renal hemodynamics including papillary plasma flow, measured by the albumin-accumulation technique, and papillary tissue solute content were determined during hydropenia in 13 anesthetized sodium-replete and 10 sodium-depleted dogs. Salt depletion induced a significant rise in plasma renin activity and aldosterone without potassium depletion. Mean arterial pressure, GFR, and renal blood flow were similar in sodium-depleted and sodium-replete dogs. Despite a similar distribution of cortical blood flow (measured by the microsphere method) in the two groups, papillary plasma flow was markedly reduced in sodium-depleted dogs (8.8 +/- 1.7 vs. 22.8 +/- 1.9 ml X min-1 X 100 g-1 in sodium-replete dogs), associated with a significant decrease in renal sodium excretion. Furthermore, papillary osmolality and sodium concentration were significantly greater in sodium-depleted dogs. Ultrastructure examination revealed smooth muscle cells surrounding the efferent arterioles and pericytes with contractile potential encircling descending vasa recta. These results suggest that included in the complex hemodynamic adjustment to chronic sodium depletion is a significant reduction in inner medullary blood flow that may be important in maintaining enhanced papillary solute concentration. In addition, the anatomy of the medullary vasculature is compatible with regional regulation of medullary blood flow.

Hormonal Regulation of Renal Salt Excretion

T SHOULD BE obvious from reading many of the previous articles in this issue of Seminurs in Nephrulogy that the role the kidney plays in the regulation of salt (NaCl) excretion is critical to the maintenance of normal sodium balance. Conversely, the development of sodium retention and edema formation is associated with a variety of disease states and disorders of renal salt excretion. The purpose of this present article will be to review those hormones presently felt to either definitely or possibly play a role in the regulation of salt excretion at the level of the kidney. Emphasis has been placed on relatively recent findings in this rapidly evolving field. In general there are two possible ways that hormonal actions may alter the rate of renal salt excretion: (A) a change in renal hemodynamics may lead to a change in either glomerular filtration rate, the dynamics of peritubular capillary reabsorption in the regions of the proximal tubule,’ or alterations of papillary plasma flow,* all of which may indirectly change the amount of salt excreted by the kidney, or (B) hormones may directly affect the transtubular salt transport at one or several segments of the nephron. The hemodynamic issues are reviewed in considerable detail in the article by Baylis in this issue and thus will not be reviewed here.

Papillary plasma flow in rats. II. Hormonal control.

Papillary plasma flow (PPF) was measured by the albumin accumulation technique in Wistar rats. PPF was significantly lower in male (293 +/- 5 microliter X min-1 X g-1) than in female (499 +/- 17) rats. Castration in male rats increased PPF; testosterone administration in gonadectomized rats returned PPF to control. Acute indomethacin administration equalized PPF in both sexes to low values close to those found in normal males (320 +/- 5 in males, 326 +/- 17 in females). Conversely, captopril administration equalized PPF in both sexes by raising PPF in males (505 +/- 21) without significant change in females (526 +/- 88). Dehydration decreased PPF slightly in males (255 +/- 28) but more markedly in females (349 +/- 11). This decrease was prevented by captopril administration (520 +/- 34 and 609 +/- 61 in males and females, respectively). In captopril-treated male rats, angiotensin II (AII) was continuously infused by osmotic minipumps at a rate of 5 micrograms/h. This did not restore PPF (405 +/- 12) to basal values. In contrast, AII infusion together with indomethacin administration completely restored PPF (322 +/- 22) in captopril-treated rats whereas indomethacin alone did not normalize PPF (425 +/- 18). We suggest that male sex hormones and AII decrease PPF, and account for the low PPF measured in male rats. Vasodilator PGs are involved in the high PPF found in female rats. The vasodilator action of captopril on papillary circulation is explained by both decreased AII formation and increased PG synthesis.

Effects of diuretics on inner medullary hemodynamics in the dog.

Although the hemodynamic effects of diuretics have been studied extensively, their effects on inner medullary blood flow remain unknown. In the present study, renal hemodynamics, including papillary plasma flow measured by the albumin accumulation technique, and associated alterations in papillary tissue solute content were determined in anesthetized, hydropenic dogs and during euvolemic diuresis induced by furosemide (3 mg/kg plus 2 mg/kg per hr, iv), ethacrynic acid (3 mg/kg plus 2 mg/kg per hr, iv) or chlorothiazide (10 mg/kg plus 10 mg/kg per hr, iv). Renal blood flow increased significantly after furosemide and ethacrynic acid and decreased significantly after chlorothiazide. Sixty minutes after diuretic administration, papillary plasma flow was 10.8 +/- 1.0 (mean +/- SE) in six furosemide- and 11.3 +/- 2.6 ml/min per 100 g in six ethacrynic acid-treated dogs, both significantly lower than in eight normal or eight chlorothiazide-treated dogs [26.4 +/- 2.6 and 26.7 +/- 2.7 ml/min per 100 g, respectively (P less than 0.01)]. A similarly low papillary plasma flow was also noted 10 minutes after diuretic administration in five furosemide and four ethacrynic acid dogs (13.6 +/- 2.3 and 13.4 +/- 1.8 ml/min per 100 g, respectively). In furosemide and ethacrynic acid dogs, papillary osmolality and sodium content were significantly lower than those in normal or chlorothiazide dogs. In normal and chlorothiazide dogs, papillary sodium content was similar, with a significantly reduced papillary osmolality in the latter. At the time papillary plasma flow was measured, extracellular fluid volume was similar among the four groups of dogs; however, plasma renin activity increased significantly in furosemide and ethacrynic acid dogs (P less than 0.01) and remained unchanged in normal and chlorothiazide dogs. Furthermore, papillary plasma flow was restored to normal (25.3 +/- 3.9 ml/min per 100 g) in five dogs in which furosemide was infused during angiotensin II blockage with saralasin, despite a similar diuresis and natriuresis as the other furosemide group. These data demonstrate that after administration of furosemide, ethacrynic acid and chlorothiazide, regulation of papillary plasma flow is independent of renal blood flow, and suggest that angiotensin II may play a role in the reduced papillary plasma flow in furosemide and ethacrynic acid dogs.

Effect of an Anteroventral Third-Ventricle Lesion on Sodium Chloride Hypertension in Dahl S Rats

1. After a lesion had been made in the anteroventral third ventricle (AV3V), Dahl S rats received daily injections of either pitressin (500 m-units/kg) or vehicle during 10 weeks of high (8%) NaCl diet. Rats with sham lesions served as controls. The blood pressure in sham-lesion rats receiving vehicle was 189 mmHg after 10 weeks of high NaCl diet. Lesion rats given vehicle showed a 60% smaller increase in blood pressure than sham-lesion rats (P &amp;lt; 0.001), the blood pressure averaging 161 mmHg at 10 weeks. 2. Lesion rats given pitressin also showed a smaller increase in blood pressure than sham-lesion rats (P &amp;lt; 0.05), but the final blood pressure averaged 176 mmHg and was significantly higher than that of lesion rats given vehicle (P &amp;lt; 0.025). Pitressin injections corrected the hypernatraemia in lesion rats. 3. In another experiment, the effect of the AV3V lesion on the renal papillary plasma flow (RPPF) in Dahl S rats was studied. Dahl S rats have a lower RPPF than Dahl salt-resistant (R) rats even on a low NaCl intake. The AV3V lesion increased the RPPF by 14% in S rats (P &amp;lt; 0.025). 4. These findings suggest that NaCl-induced hypertension in Dahl S rats requires the integrity of the AV3V region for its full expression, and the ability of the AV3V lesion to attenuate the NaCl-induced hypertension in Dahl S rats is partly related to the attenuation of vasopressin release. Moreover, the AV3V lesion partly corrected one of the characteristic features of Dahl S rats: the reduction in RPPF compared with Dahl R rats on a low NaCl intake.

Effect of an anteroventral third ventricle lesion on NaCl hypertension in Dahl salt-sensitive rats

An anteroventral third ventricle (AV3V) lesion in the brain prevents several forms of experimental hypertension. The present experiment was designed to determine whether the AV3V lesion prevents NaCl-induced hypertension in Dahl salt-sensitive (S) rats and whether attenuation of vasopressin release reported in lesioned rats contributes to the protective effect of the AV3V lesion against hypertension. After the AV3V lesion Dahl S rats received daily injections of either vasopressin (pitressin tannate, 500 mU/kg) or vehicle during 10 wk of 8% high-NaCl diet. Sham-lesioned rats served as controls. The blood pressure in sham-lesioned rats receiving vehicle was 189 mmHg after 10 wk of high-NaCl diet. Lesioned rats given vehicle showed a significantly smaller increase in blood pressure than sham-lesioned rats (P less than 0.001), the blood pressure averaging 161 mmHg at 10 wk. Lesioned rats given vasopressin also showed a smaller increase in blood pressure than sham-lesioned rats (P less than 0.05), but the final blood pressure averaged 176 mmHg and was significantly higher than that of lesioned rats given vehicle (P less than 0.025). Vasopressin injections corrected the hypernatremia in lesioned rats. In another experiment the effect of the AV3V lesion on the renal papillary plasma flow (RPPF) in Dahl S rats was studied. Dahl S rats have a lower RPPF than Dahl salt-resistant (R) rats even on a low-NaCl intake. The AV3V lesion increased the RPPF by 14% in S rats (P less than 0.025). These findings suggest that NaCl-induced hypertension in Dahl S rats requires the integrity of the AV3V region for its full expression, and the ability of the AV3V lesion to attenuate the NaCl-induced hypertension in Dahl S rats is partly related to the attenuation of vasopressin release. Moreover, the AV3V lesion partly corrected one of the characteristic features of Dahl S rats, the reduction in RPPF, when compared with Dahl R rats, with both strains on a low-NaCl intake.

Papillary plasma flow in rats. I. Relation to urine osmolality in normal and Brattleboro rats with hereditary diabetes insipidus.

Papillary plasma flow (PPF) was measured by the albumin accumulation technique in rats of the Brattleboro strain with or without diabetes insipidus (DI and HZ respectively) and in Wistar rats. Measurements were also performed in DI rats receiving antidiuretic hormone for 30 min or 5 days and in dehydrated Wistar rats. PPf in HZ control and Wistar control rats was similar to previously published measurements. In contrast PPF was significantly higher in DI rats (461 +/- 26 microliters/min . g versus 263 +/- 28 in HZ) and decreased significantly after acute ADH administration. It returned to control values after prolonged ADH administration (262 +/- 40). Plasma flow entering the papilla was inversely correlated with urine osmolality up to 1000 mosmol/kg H2O. Further increases in urine concentration (dehydration of Wistar rats) did not modify further PPF (255 +/- 28 versus 270 +/- 16 in non dehydrated Wistar). PPF might be influenced indirectly by ADH or prostaglandins and seems to depend on the osmotic environment of the papilla up to a certain limit. The factors which maintain PPF at a given minimum level with further increases in urine concentration are not known.

The influence of renal prostaglandins, central nervous system and NaCl on hypertension of Dahl S rats.

SUMMARY 1.Kidney factors and central nervous system (CNS) factors appear to have powerful influences on NaCl-induced hypertension. In quick-frozen kidneys the prostaglandin E2 (PGE2) concentration in the renal papilla is 60% lower in Dahl S rats than in Dahl R rats (17 ng/100 mg vs 42 ng/100 mg; P<0.01) when both S and R rats are on a 0.3% low NaCl diet. When S and R rats eat a 4% high NaCl diet for 4 weeks or 11 weeks, the PGE2 concentration doubles in both strains (P<0.05) but the papillary PGE2 concentration in the S rats is always about half that in the R rats (P<0.01). 2.Through effects on Na excretion and papillary plasma flow, the low PGE2 in S papillas may account in part for the large rises of blood pressure in S rats after eating a high NaCl diet. This proposition was explored by utilizing high fat diets with either normal or high linoleic acid content. Arachidonic acid is the precursor of PGE2 and linoleic acid is the precursor of arachidonic acid. It turned out that the low PGE2 level in S papillae could be tripled by a diet high in linoleic acid. Sixteen S rats on a 16 week diet with 5% NaCl/1.5% linoleic had a mean papillary PGE2 level of 30 compared to a level of 89 in fifteen other S rats on a diet with 5% NaCl/16% linoleic. The 16% high linoleic diet tripled the PGE2 concentration in S papillae (P< 0.005). It also increased the PGE2 concentration in R papillae 2.5 times, 137 vs 53 (P<0.02). On either high or normal linoleic diets the PGE2 in S papillae was always at least 35% less than that in R papillae. However the 16% high linoleic diet did raise the papillary PGE2 level in S rats up to that found in normal rats on regular rat chow of equivalent NaCl content. Moreover this change in PGE2 level was associated with greatly reduced blood pressure rises in S rats. 3. The blood pressures of S rats on a 5% NaCl/1.5% linoleic diet began to rise after 5 weeks on the diet and reached 183 mmHg after 16 weeks. The blood pressures of S rats on a 5% NaCl/16% linoleic diet did not begin to rise until 12 weeks on the diet and reached only 166 after 16 weeks. The high linoleic diet greatly delayed the onset of the rise in blood pressure and significantly reduced the ultimately attained level (P< 0.001). In fact, on a low 0.3% NaCl diet, S rats of comparable age will reach approximately the same mildly hypertensive level of 166. Thus in S rats the high linoleic diet brings papillary POE2 up to normal and also prevents the large rises in blood pressure usually related to a high NaCl intake. These two changes may well be causally related. 4. The CNS also influences NaCl hypertension in S rats. Bilateral electrolytic lesions of the paraventricular nuclei bordering the third brain ventricle cause S rats to attain only half of the NaCl-induced hypertension seen in sham-lesioned S rats (163 vs 197 mmHg, P< 0.001). Destroying catecholaminergic neurons in the brain of S rats using 6-hydroxydopamine put into the lateral brain ventricle also abolishes half of the NaCl hypertension (165 vs 210; P<0.001). Bilateral lesions of the suprachiasmatic nuclei near the third brain ventricle significantly worsen NaCl hypertension in S rats (blood pressure 201 with SCN lesions vs blood pressure 186 with sham lesions, P<0.001). Thus the kidney, the CNS and sodium influence the degree of hypertension in the Dahl S rat.