Renal responses to acute volume expansion and atrial natriuretic factor in streptozotocin-induced diabetic rats.

The purpose of this study was to determine whether diuretic and natriuretic effects are altered in response to volume expansion (VE) and atrial natriuretic factor (ANF) in 4-week diabetic rats. Diabetes was induced in two groups of male Sprague Dawley rats using streptozotocin (STZ), while a control group of rats was treated with vehicle alone, four weeks prior to the experiment. One group of diabetic rats was treated daily with insulin for the four weeks prior to the experiment. Before, during and after VE (1.2 ml/min for 15 min), urine flow and sodium excretion were measured from innervated and denervated kidneys in the three groups of anesthetized rats. Then the renal response to infusion of ANF (0.25 microgram/kg/min for 15 min) were observed in these rats. During VE, urine flow and sodium excretion from innervated kidneys, but not from denervated kidneys, were significantly lower in diabetic rats than those in control rats. Urine flow and sodium excretion from innervated as well as denervated kidneys of the diabetic rats failed to increase compared to the control rats in response to ANF. Correcting the diabetic condition with insulin (third group) rectified the blood glucose levels and the blunted responses to either VE or ANF. At the initial level, glomerular filtration rate (GFR) was not significantly different among the three groups. During VE and ANF infusion, changes in GFR was not parallel to changes in excretory parameters, therefore the hemodynamic change may not be the main reason for the blunted renal responses in diabetic rats. This study demonstrates that: (1) the volume reflex is blunted in the 4-week diabetic rats, which is in part due to the presence of tonic renal nerve activity, (2) renal responses to ANF are blunted in the 4-week diabetic rats, and (3) insulin treatment in diabetic rats normalizes the altered renal responses to either acute volume expansion or ANF.     

Interactions between the sympathetic nervous system and atrial natriuretic factor in the control of renal functions

We studied neural influences on the renal actions of atrial peptides in anaesthetized cats by comparing the response to atrial natriuretic factor (ANF) infusion in the innervated kidney and in the contralateral surgically denervated kidney. During ANF infusion arterial pressure decreased, the heart rate did not change and blood flow to both kidneys increased slightly. Vascular conductances became slightly but significantly higher in the denervated kidneys than in the controls. In both kidneys, the glomerular filtration rate increased transiently and significantly. Inhibition of renin release was more prompt and larger in the innervated than in the denervated kidneys. ANF infusion caused a significant increase in sodium and water excretion from both the innervated and denervated kidneys. However, the diuretic and natriuretic effect in the innervated kidneys, although proportionally greater than that in the denervated kidneys, was of shorter duration and subsided after 20 min of ANF infusion. Efferent renal nerve activity did not change during the initial 10 min of ANF infusion but thereafter increased progressively and significantly. We conclude that the effects of atrial peptides on renin release and excretory functions are influenced by renal nerve activity.     

Effect of Atrial Natriuretic Factor [ANF (arg 101–Tyr 126)] on Kallikrein and Cyclic GMP in the Renovascular Hypertensive Rat

The intravenous injection of an ED₅₀ natriuretic dose (1 μg) of synthetic ANF decreases blood pressure by 61 ± 6 mmHg in 2-K, 1-C, and of 45 ± 6 mmHg in 1-K, 1-C hypertensive rats, which was positively correlated with its initial level only in the 2-K, 1-C group. The hypotensive response lasted longer in the latter (> 40 min) than in normotensive sham-operated rats. No difference in duration was seen between 1-K, 1-C hypertensive and its uninephrectomized normotensive controls. The diuretic response to ANF was higher in 2-K, 1-C rats. No hematocrit changes were observed in any group. ANF induced a rise in urinary kallikrein in all groups but the 1-K, 1-C. Urinary kallikrein excretion was positively correlated with natriuresis in normotensive but not in hypertensive groups. ANF induced an increase in urinary cGMP excretion in all groups but the 1-K, 1-C, and an increase in plasma cGMP in the normotensive sham-operated animals.

Our results suggest that the fall in blood pressure induced by synthetic ANF could be due to vasodilatation, a drop in cardiac output cannot, however, be eliminated. Whether the hypotensive effect of ANF is mediated by cGMP remains to be demonstrated.     

Retardation of the development of hypertension in DOCA-salt rats by renal denervation

To determine the importance of the renal nerves in DOCA-salt hypertension, either renal denervation or a sham-operation was carried out on both DOCA-salt-treated and non-DOCA-treated rats. The systolic blood pressure of the non-DOCA rats remained within normotensive levels, in which the difference in blood pressure levels between the renal denervated and the sham-operated groups was not significant. On the other hand, the blood pressure of the rats treated with DOCA, and having intact renal nerves, began to rise by the end of the first week and rose consistently thereafter, whereas, in the renal denervated DOCA-salt rats, the blood pressure started to rise by the second week and then proceeded to increase gradually. The differences between the sham and the denervated rat groups were significant throughout the four weeks. The mean arterial pressure, directly measured from the caudal artery of conscious rats during the fourth week of this study, was 166 +/- 7 mmHg in the sham-operated and 129 +/- 4 mmHg in the renal-denervated rats (the data having an 1% significant difference). To test the effects of renal denervation on the natriuresis, pentobarbital-anesthetized rats were infused intravenously with physiological saline. The renal denervated rats which had received DOCA excreted more sodium than did the sham-operated rats. When the rats were later anesthetized with urethane to allow intracisternal injections of hypertonic saline, the mean blood pressure in renal denervated rat groups was again lower than that of the sham-denervated rat groups. However, subsequent intracisternal injections of 5% saline produced similar pressor responses as well as tachycardia in both DOCA groups.(ABSTRACT TRUNCATED AT 250 WORDS)     

A comparison of the action of atriopeptin III on renal function in normal and DOCA-salt hypertensive rats

Administration of atriopeptin III (125, 250 and 500 ng/kg, intravenously) into pentobarbitone anaesthetized normotensive and DOCA-salt hypertensive rats had no effect on blood pressure or renal haemodynamics. Urine flow and absolute and fractional sodium excretion were increased by 48-90% from the lowest to the highest dose of atriopeptin III in the normotensive group, but were increased by over twice these amounts in the DOCA-salt hypertensive rats. Fractional lithium excretion and calculated proximal tubular fluid reabsorption were unaffected by the peptide in the normotensive rats, but in the hypertensive group atriopeptide III increased fractional lithium excretion by 25-50% and decreased proximal tubular reabsorption to a similar extent. Beyond the proximal tubule there were similar increases in fractional and absolute fluid handling in both groups of rats. These results demonstrated that in DOCA-salt hypertension there was increased sensitivity to the natriuretic activity of atriopeptin III which appeared to result from an increased responsiveness of the proximal tubule.     

Increased prostaglandin synthesis in the unclipped kidney of one-kidney, one clip hypertensive rats

Reversal of one-kidney, one clip (1-K, 1C) hypertension by removal of the renal artery clip is accompanied by increased renal and vascular prostaglandin (PG) production. It was postulated that PG biosynthesis is stimulated in the unclipped hypertensive kidney. In order to test this hypothesis, we compared urinary excretion of PGE2 and 6-keto-PGF1 alpha (a breakdown product of PGI2) in perfused kidneys isolated from 1-K, 1C hypertensive rats, 1-K, sham-clipped rats and 1-K, 1C rats which had failed to become hypertensive. Urine was collected over 15 min periods at perfusion pressures of 100, 150 and 200 mmHg. At perfusion pressures of 100 and 150 mmHg there was no significant difference in PGE2 excretion between the three groups. In contrast, 6-keto-PGF1 alpha excretion at 150 mmHg was higher in the hypertensive rats compared with the sham-clipped (P less than 0.05) and failed hypertensive (P less than 0.01) rats. At 200 mmHg, both PGE2 and 6-keto-PGF1 alpha were significantly higher in the hypertensive rats than in the control groups. These increases in PG excretion were clearly dissociated from changes in urinary flow rates. The findings support the hypothesis of increased synthesis of renal vasodilatory and natriuretic PGs in 1-K, 1C hypertension which is particularly evident at higher perfusion pressures, such as may be encountered when the hypertensive kidney is unclipped and exposed to high arterial pressure.     

Suppression of renal sympathetic activity with potassium supplement in DOCA-salt rats

We studied the involvement of renal sympathetic nervous system activity in the antihypertensive and natriuretic effects of potassium supplement in DOCA-salt treated rats. Systolic blood pressure of DOCA-salt rats rose substantially, reaching 181 +/- 3 mmHg after 4 weeks of DOCA-salt administration. In contrast, the supplement of 1% KCl solution attenuated the development of the hypertension until the fourth week (120 +/- 1 mmHg). After the 4-week treatments, renal norepinephrine turnover rate was calculated from the decline in specific activity after the injection of dl-3H-norepinephrine. It was markedly accelerated in DOCA-salt rats as compared to control rats. In contrast, 1% KCl supplement significantly restored to normal the increased renal norepinephrine turnover rate in DOCA-salt rats. Taken together, evidence presented suggests that the normalization of the increased renal sympathetic tone may be involved in the natriuretic and antihypertensive effects of potassium supplement in DOCA-salt hypertensive rats.     

Effect of Renal Denervation on the Development of Cellophane-Wrap Hypertension in Rabbits

The development of hypertension in rabbits with bilateral cellophane wrapping of the kidneys was studied in animals with and without surgical denervatton of the kidneys. Mean arterial pressure was measured before and 14 and 28 days after surgery. After 14 and 28 days of wrapping, mean arterial pressure had increased 12 ± 3 mmHg and 31 ± 3 mmHg in rabbits with innervated kidneys and 7 ± 2 mmHg and 26 ± 2 mmHg in rabbits with denervated kidneys, respectively. The increases in arterial pressure were significantly less in the denervated animals. In sham wrap animals, renal denervation also resulted in significantly lower arterial pressure than in sham wrap+sham denervated rabbits. Noradrenaline concentration of denervated kidneys averaged only 4% of that measured in kidneys subjected to sham denervation. The results show that renal denervation slightly attenuated the degree of hypertension developed following renal wrapping. Since renal denervation produced a similar small decrease in arterial pressure in normotensive rabbits it is suggested that the effect is non-specific and probably due to loss of efferent renal sympathetic nerves.     

Attenuated cardiovascular and sympathetic nerve responses to aortic nerve stimulation in DOCA-salt hypertensive rats

In order to verify, whether baroreflex sensitivity is changed centrally in DOCA-salt hypertension, the left aortic depressor nerve (ADN) was electrically stimulated in DOCA-salt hypertensive rats. After 3 weeks, tail-cuff systolic pressure was significantly higher in DOCA-salt treated rats than in untreated rats (169 +/- 4 versus 130 +/- 4 mmHg, respectively; P less than 0.001). After cutting both ADN and the carotid sinus nerves, the central cut end of the left ADN was electrically stimulated and frequency dependent depressor, bradycardic and sympatho-inhibitory responses were elicited in both control and DOCA-salt hypertensive rats. However, these responses were significantly smaller in DOCA-salt hypertensive rats than in normotensive controls. Bradycardic and sympatho-inhibitory responses to i.v. injection of norepinephrine were also blunted in DOCA-salt hypertensive rats. These findings suggest that baroreflexes were centrally attenuated in DOCA-salt hypertensive rats and possibly contribute to overall baroreflex attenuation.     

Hemodynamic and Renal Effects of Atrial Natriuretic Factor (99-126) in Volume Expanded Sheep

ABSTRACT

The renal and hemodynamic effects of atrial natriuretic factor 99-126 (ANF) were examined in hypervolemic sheep and the results compared to responses previously observed in normal isovolemic sheep. Infusion of 500ml dextran over 60 min increased blood pressure by 6 ± 2 mmHg, associated with increases in cardiac output and stroke volume. No change was seen in heart rate nor total peripheral resistance. Subsequent infusion of ANF at 100 μg/h for 60 min reduced blood pressure by 6 ± 1 mmHg and decreased stroke volume and cardiac output. There was no change in heart rate. Total peripheral resistance decreased slightly, to a similar degree to that seen after control infusion of 500 ml dextran. Moderate increases in urine volume, sodium and chloride excretion were seen after infusion of dextran and subsequent infusion of ANF markedly enhanced these renal effects. The renal changes produced by ANF in volume expanded sheep were significantly greater than those observed in normal sheep. Although normal sheep are more sensitive to the hemodynamic than to the renal effects of ANF, after dextran pretreatment there was enhancement of the renal responses with little change in the effects on blood pressure.     

Exaggerated natriuretic response to atrial natriuretic factor in rats developing spontaneous hypertension

The present study was designed to evaluate the renal response to atrial natriuretic factor (ANF) in young rats developing spontaneous hypertension (SHR) and compare this response to age-matched, normotensive controls (WKY) and adult animals. At 6 weeks of age, intravenous infusion of ANF (0.25 micrograms/kg min) in anesthetized, euvolemic rats produced a significantly larger natriuresis and diuresis in SHR compared with WKY rats; this strain difference was not observed in rats 11 weeks of age. SHR showed no age-related change in the natriuretic response to ANF, whereas adult WKY rats exhibited a greater response than young WKY rats. To determine the effect of renal perfusion pressure on the magnitude of the renal response to ANF, additional groups of 6- and 11-week-old SHR were studied while renal perfusion pressure was lowered acutely by aortic constriction (SHR-AC) to values similar to age-matched WKY rats. In young rats, the diuretic and natriuretic response to ANF was greatest in SHR, intermediate in SHR-AC, and lowest in WKY rats. In adult animals, the natriuretic and diuretic response was similar in SHR and WKY rats and tended to be less in SHR-AC. These results in both 6- and 11-week-old SHR are consistent with previous reports that the magnitude of the response to ANF is directly related to acute changes in renal perfusion pressure.(ABSTRACT TRUNCATED AT 250 WORDS)     

Role of sympathetic nerve activity and natriuresis in the antihypertensive actions of potassium in NaCl hypertension

Although the precise mechanism of the antihypertensive action of potassium remains controversial, the natriuretic property of potassium is thought to play an important role. Since the renal nerves have been shown to control urinary sodium excretion, the present study was performed to clarify the role of the sympathetic nervous system in the antihypertensive effect of potassium supplements in DOCA-salt hypertensive rats and in salt-sensitive hypertensive patients. Supplements of a 0.2% or a 1% KCl were able to moderate the development of the DOCA-salt hypertension dose-dependently, in combination with natriuresis. Renal norepinephrine turnover was markedly accelerated in the DOCA-salt rats as compared with the control rats, but the potassium supplements normalized it. Eleven patients, who had taken the potassium supplement (96 mEq/day) on a high-sodium diet, showed a lesser increase in mean blood pressure with sodium loading than 12 patients who did not take the potassium supplement. With a high-sodium diet, the potassium-supplemented patients retained less sodium and showed a lesser increase of plasma volume and cardiac output, and their adrenergic nervous activity was relatively lower during the early period of salt loading. Moreover, in salt-sensitive patients the potassium supplement was more effective for preventing a rise in blood pressure with sodium loading than in non-salt-sensitive ones. These results suggest that potassium may attenuate the rise in blood pressure during the DOCA-salt treatment in the rat and during sodium loading in salt-sensitive patients, mainly as a result of inhibiting sodium retention due to increased renal sodium excretion.(ABSTRACT TRUNCATED AT 250 WORDS)     

The Role of Kinins and Atrial Natriuretic Peptide on the Renal Effects of Neutral Endopeptidase Inhibitor in Normotensive and Hypertensive Rats

To further elucidate the renal effects of NEP inhibition, we employed NEP inhibitor UK 73967 (UK), with or without a kinin receptor antagonist Hoe 140 (Hoe), in Sprague-Dawley normotensive rats and DOCA-salt hypertensive rats.

In Sprague-Dawley rats: 1) injected UK significantly decreased NEP, and increased kinins, urine volume (UV) and urinary sodium excretion (UNaV), while none of the variables changed with vehicle treatment; 2) no difference was found in plasma ANP between the vehicle and UK groups; and 3) Hoe canceled the increases of UV and UNaV caused by UK.

In DOCA-salt rats: 1) infused UK significantly decreased NEP, and increased UV and UNaV, while UV and UNaV were slightly decreased, and NEP did not change with vehicle treatment; 2) plasma ANP was significantly higher in UK group than in the vehicle group; and 3) Hoe could not abolish the increase of UV and UNaV induced by UK.

These data indicate that the contributions of renal kinins and plasma ANP to the diuretic and natriuretic mechanisms of NEP inhibition may differ between Sprague-Dawley normotensive rats and DOCA-salt hypertensive rats.     

Function of the isolated perfused kidneys from young or adult rats with post-DOCA-salt hypertension.

The function of isolated perfused kidneys in post-DOCA phase of DOCA-salt hypertension was evaluated in rats subjected to DOCA-salt treatment either from youth or only in adulthood. Post-DOCA-salt hypertension was more severe in young than in adult animals. Kidneys isolated from young post-DOCA-salt hypertensive rats had higher renal vascular resistance when compared to adult ones. Perfusion of isolated kidneys over a wide range of perfusion pressure (110-170 mm Hg) has shown similar decrease of glomerular filtration, filtration fraction, diuresis and natriuresis in both age groups of DOCA-salt treated groups. Perfusion pressure-sodium excretion curves had reduced slope and were shifted to the right in both hypertensive groups, indicating huge glomerular damage. Nevertheless, the relative difference in glomerular filtration and sodium excretion between hypertensive rats and age-matched normotensive controls was always greater in younger animals. These results suggest that the more pronounced changes in glomerular hemodynamics and filtration could be involved in higher blood pressure-response of young animals to DOCA-salt treatment.     

Function of the Isolated Perfused Kidneys from Young or Adult Rats with Post-Doca-Salt Hypertension

The function of isolated perfused kidneys in post-DOCA phase of DOCA-salt hypertension was evaluated in rats subjected to DOCA-salt treatment either from youth or only in adulthood. Post-DOCA-salt hypertension was more severe in young than in adult animals. Kidneys isolated from young post-DOCA-salt hypertensive rats had higher renal vascular resistance when compared to adult ones. Perfusion of isolated kidneys over a wide range of perfusion pressure (110–170 mm Hg) has shown similar decrease of glomerular filtration, filtration fraction, diuresis and natriuresis in both age groups of DOCA-salt treated groups. Perfusion pressure-sodium excretion curves had reduced slope and were shifted to the right in both hypertensive groups, indicating huge glomerular damage. Nevertheless, the relative difference in glomerular filtration and sodium excretion between hypertensive rats and age-matched normotensive controls was always greater in younger animals. These results suggest that the more pronounced changes in     

Influence of prostaglandins on papillary blood flow and pressure-natriuretic response

The present study examined whether renal prostaglandins influence the pressure-natriuretic response by altering medullary hemodynamics or renal interstitial pressure. The diuretic and natriuretic responses to changes in renal perfusion pressure were compared in control rats (n = 15) and in rats receiving either meclofenamate (2 mg/kg, n = 9) or indomethacin (2 mg/kg, n = 4). In control rats, urine flow and sodium excretion increased from 10 +/- 2 to 118 +/- 10 microliters/min/g kidney wt and from 1.8 +/- 0.3 to 21.0 +/- 1.5 mueq/min/g kidney wt, respectively, when renal perfusion pressure was increased from 109 to 167 mm Hg. Urinary excretion of prostaglandin E2 and thromboxane B2 increased significantly by 152% and 190%, respectively. Meclofenamate lowered thromboxane B2 and prostaglandin E2 excretion and prevented the increase in eicosanoid excretion produced by elevations in perfusion pressure. The pressure-diuretic and pressure-natriuretic responses of rats given meclofenamate or indomethacin were approximately half of those observed in the control rats. Papillary blood flow increased 21% and renal interstitial pressure rose from 5.0 +/- 0.7 to 8.2 +/- 0.7 mm Hg in control rats when pressure was elevated from 100 to 150 mm Hg. Meclofenamate and indomethacin lowered papillary blood flow and renal interstitial pressure and blunted the increases in these values produced by elevations in perfusion pressure. These results support the view that renal prostaglandins modulate the pressure-natriuresis relation by altering renal medullary hemodynamics and suggest that an intact renal prostaglandin system is necessary for the full expression of the medullary hemodynamic and natriuretic responses to increases in renal perfusion pressure.     

Involvement of Endogenous Dopamine and Da-1 Receptors in the Renal Effects of Atrial Natriuretic Factor in Rats

The precise mechanism of the diuretic and natriuretic effects of Atrial Natriuretic Factor (ANF) is still unclear. The present study was undertaken with the aim of elucidating the mechanism of interaction between ANF, dopamine (DA) and DA receptors in the renal effects of ANF in rats. In pentobarbital anesthetized rats, ANF infusion (10 µg/kg/hour) produced marked diuresis and natriuresis which was accompanied by significant hypotension, bradycardia and also a modest increase in glomerular filtration rate However, there was no accompanying increase in urinary DA excretion during ANF infusion. Pretreatment with SCH 23390, a selective DA-1 receptor antagonist caused significant attenuation of the diuretic and natriuretic effects of ANF whereas the hemodynamic changes produced by ANF were still evident in SCH 23390 treated animals. Plasma ANF levels were elevated to the same magnitude in both the control and SCH 23390 treated groups. Pretreatment with carbidopa, a dopa decarboxylase inhibitor also significantly blunted the diuretic and natriuretic effects of ANF. The antagonism of the ANF-induced diuresis and natriuresis by SCH 23390 and carbidopa was comparable in magnitude. These results suggest that endogenous DA, via activation of DA-1 receptors plays a permissive role in the renal effects of ANF, perhaps by enhancing tubular responsiveness to ANF. However, there does not appear to be a stimulatory effect of ANF on renal DA production or release.     

Lifetime Treatment with Captopril Improves Renal Function in Spontaneously Hypertensive Rats

Lifetime treatment with captopril prevents the development of hypertension in spontaneously hypertensive rats (SHR). This study tests the hypothesis that compared to untreated hypertensive SHR, captopril-treated SHR display similar diuretic and natriuretic responses to an isotonic saline infusion despite significantly lower arterial pressure. Eight-week-old, male SHR were instrumented with femoral arterial, venous, and bladder catheters. Forty-eight hours later, each rat was infused intravenously with an isotonic saline load (5% of body weight; 0. 5 ml/min). Lifetime captopril-treated SHR and untreated control SHR displayed nearly identical natriuretic and diuretic responses to the saline infusion. Thus, although lifetime captopril treatment significantly reduces mean arterial pressure in SHR, renal excretory responses appear to be unaltered. Moreover, histological examination of the kidneys of the lifetime captopril-treated SHR did not reveal significant structural damage in the kidneys at either 8 weeks of age or at 12 months of age. Together, the data suggest that lifetime captopril treatment does not adversely affect renal function and structure in SHR.     

Glomerular and vascular atrial natriuretic factor receptors in cardiomyopathic hamsters: correlation with the peptide biological effects

STUDY OBJECTIVE--The aim was to study glomerular and vascular atrial natriuretic factor (ANF) receptors and their relationship with the post-receptor effects of the peptide in experimental heart failure. DESIGN--Binding sites ANF were studied in renal glomerular and mesenteric artery membranes. The natriuretic and relaxing effects of ANF were evaluated in the intact animal and in noradrenaline precontracted aortic strips respectively. Plasma and tissue ANF levels were also assessed. EXPERIMENTAL MATERIAL--The study was performed on cardiomyopathic (UM-X7.1) hamsters (n = 15) with a moderate degree of heart failure. Age matched Golden Syriam hamsters (n = 15) were used as controls. MEASUREMENTS AND MAIN RESULTS--Cardiomyopathic hamsters presented lower blood pressure, body weight, and plasma Na+, and higher heart weight than normal hamsters. Plasma ANF (1-98) and (99-126) levels and ventricular ANF content were higher in cardiomyopathic hamster than in controls. ANF and frusemide decreased blood pressure, and increased diuresis and natriuresis in normal hamsters. The blood pressure reduction by ANF in cardiomyopathic hamsters was approximately of the same magnitude as in normal hamsters but their renal response was blunted. The blood pressure lowering effect of frusemide was similar in both cardiomyopathic and normal hamsters, but the diuretic and natriuretic responses were greatly reduced in the former. Glomerular ANF receptor density was higher and receptor affinity was lower in cardiomyopathic hamsters than in controls. Noradrenaline precontracted vascular strips from cardiomyopathic hamster were more sensitive to the relaxant effect of ANF than those from controls. No differences in either density or affinity of vascular receptor were observed. CONCLUSIONS--The results suggest that the renal hyporesponsiveness of cardiomyopathic hamsters to ANF is not due to a down regulation of glomerular ANF receptors. The fact that the natriuretic response to frusemide is also blunted suggest the involvement of other factors.     

Lifetime treatment with captopril improves renal function in spontaneously hypertensive rats

Lifetime treatment with captopril prevents the development of hypertension in spontaneously hypertensive rats (SHR). This study tests the hypothesis that compared to untreated hypertensive SHR, captopril-treated SHR display similar diuretic and natriuretic responses to an isotonic saline infusion despite significantly lower arterial pressure. Eight-week-old, male SHR were instrumented with femoral arterial, venous, and bladder catheters. Forty-eight hours later, each rat was infused intravenously with an isotonic saline load (5% of body weight; 0.5 ml/min). Lifetime captopril-treated SHR and untreated control SHR displayed nearly identical natriuretic and diuretic responses to the saline infusion. Thus, although lifetime captopril treatment significantly reduces mean arterial pressure in SHR, renal excretory responses appear to be unaltered. Moreover, histological examination of the kidneys of the lifetime captopril-treated SHR did not reveal significant structural damage in the kidneys at either 8 weeks of age or at 12 months of age. Together, the data suggest that lifetime captopril treatment does not adversely affect renal function and structure in SHR.