Eukaliuric diuresis and natriuresis in response to the KATP channel blocker U37883A: micropuncture studies on the tubular site of action.
(17/1093)
1. Systemic application of U37883A, a blocker of ATP sensitive potassium (KATP) channels, elicits diuresis and natriuresis without significantly altering urinary potassium excretion. 2. To elucidate tubular sites of action upstream to the distal nephron, micropuncture experiments were performed in nephrons with superficial glomeruli of anaesthetized Munich-Wistar-Fromter rats during systemic application of U37883A (1, 5 or 15 mg kg-1 i.v.). 3. The observed eukaliuric diuresis and natriuresis in response to U37883A at 15 mg kg-1 was accompanied by an increase in early distal tubular flow rate (VED) from 10 - 18 nl min(-1) reflecting a reduction in fractional reabsorption of fluid up to this site (FR-fluid) of 13%. The latter proposed an effect on water-permeable segments such as the proximal tubule which could fully account for the observed reduction in fractional reabsorption of Na+ up to the early distal tubule (FR-Na+) of 8% and the increase in early distal tubular Na+ concentration ([Na+]ED) from 35 - 51 mM whereas [K+]ED was left unaltered. 4. In comparison, furosemide (3 mg kg-1 i.v.), which acts in the water-impermeable thick ascending limb, elicited diuresis, natriuresis and kaliuresis which were associated with a fall in FR-Na+ of 10% with no change in FR-fluid, and a rise in [Na+]ED from 42 - 117 mM and [K+]ED from 1.2 - 5.7 mM with no change in VED. 5. Direct late proximal tubular fluid collections confirmed a significant inhibition of fluid reabsorption in proximal convoluted tubule in response to systemic application of U37883A. 6. These findings suggest that the diuretic and natriuretic effect upstream to the distal tubule in response to systemic application of U37883A involves actions on water-permeable segments such as the proximal convoluted tubule. (+info)
Urinary excretion of urodilatin is increased during pressure natriuresis in the isolated perfused rat kidney.
(18/1093)
The findings about mechanisms regulating production and excretion of urodilatin [ANP-(95-126)], a member of the atrial natriuretic peptide (ANP) family, are controversial. To elucidate a possible relationship between arterial blood pressure and renal urodilatin excretion, we studied the effects of different perfusion pressures on urine flow (UV), urinary sodium (U(Na)V), urinary potassium (U(K)V), and urodilatin excretion (U(URO)V), and the concentration of urodilatin in the perfusate (P(URO)) of isolated perfused rat kidneys. Kidneys were perfused for 180 min with constant perfusion pressures (80 and 120 mmHg, respectively; each, n = 4) in a closed circuit system. Samples of urine and perfusate were taken every 30 min. Mean UV, U(Na)V, U(K)V, and U(URO)V values were significantly higher with a perfusion pressure of 120 mmHg than with 80 mmHg, whereas P(URO) did not change significantly. Serial measurements revealed no direct relation of U(URO)V with either U(Na)V or UV. This suggests that renal perfusion pressure is a determinant of U(URO)V and that urinary and venous effluent concentrations of urodilatin (probably production) are not coupled directly and that U(URO)V and U(Na)V may dissociate during acute variations of sodium excretion and UV. (+info)
The contribution of nitric oxide to diuretic and natriuretic effects of renal kinins in normotensive rats.
(19/1093)
We have reported that diuresis and natriuresis due to increase in renal kinins induced by the neutral endopeptidase 24.11 (NEP) inhibitor were attenuated by nitric oxide (NO) synthase inhibitor. To further clarify the water-sodium excretory mechanism of renal kinins, we estimated NO2+NO3 (NOx) and cGMP in plasma and urine with and without a specific NEP inhibitor, thiorphan. P-aminohippuric acid (PAH) and inulin were injected into male Sprague-Dawley rats. Vehicle (n = 8) or thiorphan (30 mg/kg, n = 10) was injected after the control period. Mean blood pressure (MBP), plasma and urinary PAH, inulin, NOx and cGMP, urinary volume (UV) and urinary sodium excretion (UNaV) were measured before and after injection of the reagents. MBP, renal plasma flow and glomerular filtration rate were not affected by thiorphan. Plasma NOx and cGMP with thiorphan did not differ from the vehicle, while urinary NOx and cGMP increased. None of the variables were affected by vehicle. UV and UNaV were higher with thiorphan than with vehicle. Positive correlation was found between urinary deltaNOx and deltacGMP. Each urinary deltaNOx and deltacGMP was significantly correlated to both deltaUV and deltaUNaV. Urinary NOx and cGMP were increased while maintaining correlations to UV and UNaV, but plasma NOx and cGMP were not affected by thiorphan. This implies that the mechanism of water-sodium excretion induced by NEP inhibitor is mediated by renal NO. Therefore, renal NO may contribute to the diuretic and natriuretic effects of renal kinins. (+info)
Natriuretic peptides in patients with diastolic dysfunction due to idiopathic dilated cardiomyopathy.
(20/1093)
AIMS: The degree of systolic dysfunction does not always correlate with functional impairment in patients with congestive heart failure. In contrast, diastolic dysfunction correlates well with functional impairment. In heart failure, both elevation of N-terminal proatrial natriuretic peptide and B-type natriuretic peptide are markers of a poor prognosis. METHODS: We investigated 32 patients (26 male, 6 female; mean age 55+/-2 years) with dilated cardiomyopathy and sinus rhythm. M-mode echocardiography and 2D-echocardiography were carried out in each patient. Pulsed-wave Doppler inflow signals were obtained and the following parameters were measured: maximal E wave and maximal A wave velocity, E/A ratio, E wave deceleration time, A wave deceleration time. Immediately after echocardiography blood samples were collected from patients in the supine position. N-terminal proANP and brain natriuretic peptide were measured using a radioimmuno assay. RESULTS: The left ventricular ejection fraction was 34+/-1%, the left ventricular end-diastolic diameter on M-mode echocardiography was 68+/-1 mm, while left atrial diameter was 45+/-1 mm. Univariate analysis revealed a significant correlation between both left atrial diameter and ejection fraction and N-terminal proANP and brain natriuretic peptide. All transmitral Doppler parameters showed a significant correlation with N-terminal proANP and brain natriuretic peptide. On forward stepwise regression analysis, left atrial diameter and ejection fraction were able to predict both N-terminal proANP and brain natriuretic peptide. However, of the diastolic parameters only the E/A ratio remained significant. Mildly symptomatic patients differed significantly from severely symptomatic patients in all Doppler parameters. Mildly symptomatic patients had significantly lower levels of N-terminal proANP (0.571+/-0.079 vs 2.282+/-0.340 nmol. l(-1);P<0.001) and brain natriuretic peptide (51+/-14.8 vs 474.2+/- 86.8 pg. ml(-1);P<0. 001). CONCLUSION: There is a close relationship between natriuretic peptides and diastolic Doppler parameters of left ventricular filling in patients with dilated cardiomyopathy. There is also a significant difference between patients with mild and severe functional impairment regarding both natriuretic peptides and transmitral Doppler parameters. (+info)
Cardiac peptides differ in their response to exercise. Implications for patients with heart failure in clinical practice.
(21/1093)
AIMS: Cardiac peptides have diagnostic and prognostic value in heart failure. Their plasma concentrations, however, are sensitive to rapid changes in haemodynamics. As blood sampling under standard conditions is not feasible in clinical practice, it is important to know which peptides are most resistant to change. Therefore, the present study investigated the differences in response to exercise between atrial natriuretic peptide, N-terminal proatrial natriuretic peptide, brain natriuretic peptide and the recently identified N-terminal probrain natriuretic peptide. METHODS AND RESULTS: Fifty-two patients with chronic heart failure performed a symptom-limited graded bicycle exercise. Blood samples for determination of plasma concentrations of cardiac peptides were drawn at rest and at peak exercise. There was a significant difference in percentage increase in response to exercise between the four peptides (P<0.0001). N-terminal proatrial natriuretic peptide increased less than atrial natriuretic peptide (5+/-18% vs 59+/-58%;P<0.0001). The difference in increase between N-terminal probrain natriuretic peptide and brain natriuretic peptide was less distinct but still significant (24+/-24% vs 38+/-52%, P<0.05). CONCLUSIONS: Both N-terminal proatrial natriuretic peptide and N-terminal probrain natriuretic peptide increased less in response to exercise than their C-terminal counterparts. This implies that the circumstances under which blood sampling for measurements of N-terminal proatrial natriuretic peptide and N-terminal probrain natriuretic peptide should be performed are more favourable than the blood sampling conditions for atrial natriuretic peptide and brain natriuretic peptide. (+info)
Renal interstitial hydrostatic pressure and urinary sodium excretion in rats with angiotensin-converting enzyme inhibitor-induced papillary atrophy.
(22/1093)
The importance of angiotensin type-1 (AT1) receptor stimulation during renal development has recently been established in both pharmacological and knockout models. We have previously reported irreversible and progressive papillary atrophy and a reduced baseline renal interstitial hydrostatic pressure (RIHP) after neonatal angiotensin-converting enzyme (ACE) inhibition. The aim of the present study was to investigate the consequences of these abnormalities on urinary sodium excretion during acute extracellular sodium loading. Rats were treated neonatally with enalapril (10 mg kg-1 day-1) or saline control from days 3 to 23 after birth. Urinary sodium excretion was assessed in relation to mean arterial pressure (MAP) and RIHP responses in adult anaesthetised rats during moderate (1.5 and 3 % body weight) and severe (9 % body weight) saline-induced volume expansion. Control rats responded to the moderate volume expansion by increasing MAP by 16 +/- 6 % and RIHP by 40 +/- 23 %, respectively. In neonatally enalapril-treated rats, however, MAP and RIHP remained unchanged and were associated with a smaller increase in sodium excretion (44 +/- 11 % of the total amount infused versus 71 +/- 16 % for controls, P < 0.05). In contrast, severe volume expansion resulted in marked pressure rises in both the enalapril-treated group (36 +/- 12 and 112 +/- 48 % of baseline for MAP and RIHP, respectively) and the control group (34 +/- 21 and 130 +/- 34 % of baseline for MAP and RIHP, respectively). Moreover, the increases in MAP and RIHP were associated with complete excretion of the severe sodium challenge within 60 min in both treatment groups. We conclude that a RIHP response appears to be a prerequisite for adequate urinary sodium excretion in this model of papillary atrophy. Hence, an intact renal medulla is not mandatory in the renal handling of sodium during extracellular loading. (+info)
Changes in urinary water and electrolyte excretion in sodium-loaded sheep in response to intravenous infusion of arginine vasopressin.
(23/1093)
Mature sheep receiving supplements of sodium chloride into the rumen were given intravenous infusions of arginine vasopressin at rates varying from 4-6-23 pmol/min (2-10 mU/min). Infusion of the hormone led to an increase in urine flow and to increases in the amounts of sodium and chloride excreted, the effect on flow was, however, the greater so that the osmolality of the urine fell during the infusions. In sheep given intravenous infusions of a hypertonic sodium chloride solution addition of vasopressin to the infusate led to the formation of a larger volume of urine containing a higher proportion of the infused salt load compared to when the salt solution alone was given. As before the effect on flow was the greater and hence the osmolality of the urine was lower when the hormone was given. In other experiments intravenous infusion of a hypertonic sodium chloride solution at rates providing 2-8 mmol NaCl/min led to increases in urine flow and increases in sodium and chloride excretion, the size of these increases being proportional to infusion rate. Plasma vasopressin levels markedly increased during these infusions, the levels seen being similar to those seen in sheep given vasopressin in amounts which increased both urine flow and electrolyte excretion. This suggests that during hypertonic salt loading vasopressin probably contributes directly to the increases in urine flow and the increases in electrolyte excretion which are seen. Further evidence in support of this was obtained in experiments in which a greater natriuretic response was seen in sheep given a hypertonic sodium chloride solution into the carotid artery as opposed to the given a hypertonic sodium chloride solution into the carotid artery as opposed to the jugular vein and where it was shown that plasma vasopressin levels were indeed higher when the solution was given into the artery. (+info)
Diuretics shift circadian rhythm of blood pressure from nondipper to dipper in essential hypertension.
(24/1093)
BACKGROUND: Recently, we found that sodium restriction shifted the circadian rhythm of blood pressure from nondipper to dipper in patients with the sodium-sensitive essential hypertension. This study examined whether diuretics can transform the circadian rhythm of blood pressure from nondipper to dipper. METHODS AND RESULTS: We studied 21 patients with essential hypertension during both a baseline period and a period of treatment with hydrochlorothiazide (25 mg daily). The periods lasted 4 weeks each. Twenty-four hour ambulatory blood pressures were measured on the same day of the week at the end of the each period. In nondippers (n=11), but not in dippers (n=10), a significant interaction existed between diuretic therapy and nocturnal fall in systolic and diastolic blood pressure, which indicated that the degree of nocturnal blood pressure fall was affected by diuretic therapy. Nocturnal fall, which was diminished in nondippers, was restored by diuretic therapy with hydrochlorothiazide, indicating that the circadian rhythm of blood pressure shifted from nondipper to dipper patterns. CONCLUSIONS: The present study demonstrated that diuretics can restore nocturnal blood pressure decline in a manner similar to sodium restriction, which suggests that the kidneys and sodium metabolism may play important roles in the genesis of the circadian rhythm of blood pressure. Diuretic-based treatment may have an additional therapeutic advantage of reducing the risk for cardiovascular complications by transforming the circadian rhythm of blood pressure. (+info)