Atrial natriuretic peptide levels and pulmonary artery pressure awake, at exercise and asleep in obstructive sleep apnoea syndrome.
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Elevated nocturnal plasma atrial natriuretic peptide (ANP) levels were found in patients with obstructive sleep apnoea (OSA). The purpose of our study was to examine the secretion of ANP during the night and to measure changes in oxygen saturation, pulmonary artery pressure and intrathoracic pressure swings in patients with OSA. Moreover, we analysed the secretion of ANP and the pulmonary artery pressure in different behavioural states, e.g. awake, at exercise and asleep. Consecutive apnoeas in non-rapid eye movement (NREM) sleep at the beginning, middle and end of the sleep study were analysed in six patients with obstructive sleep apnoea. In addition, we measured the plasma levels of ANP. The apnoea duration was significantly longer (P< 0.05) at the middle of the sleep study than at the beginning or end. Correspondingly, the end-apnoeic oxygen saturation and end-apnoeic oesophageal pressure were both significantly lower (P< 0.05) in the middle of the sleep study than at the beginning or end. No significant differences were found in the end-apnoeic systolic transmural pulmonary artery pressure (P(PATM)) and the levels of ANP. Evaluation of the ANP levels during different behavioural states revealed that the asleep levels were slightly, but not significantly, higher than the awake levels (0.235+/-0.088 vs. 0.207+/-0.057 nmol/L). However, the highest levels were found during exercise (0.334+/-0.170 nmol/L) with a significant difference compared with the awake and asleep levels. These data suggest that volume effects may be a potent factor in liberating ANP during exercise, but the role of OSA in ANP secretion when asleep is questionable. (+info)
Measurement of changes in glomerular filtration rate induced by atrial natriuretic peptide in the rat kidney.
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This study was undertaken to improve the measurement of glomerular filtration rate (GFR) during the acute diuretic phase induced by atrial natriuretic peptide (ANP), which may indeed alter the renal clearance of inulin (GFRCL) due to dead space error. A technique to measure GFR without urine collections was therefore developed in anaesthetized rats prepared as for micropuncture. To do so, arterial blood was periodically collected and renal venous blood was withdrawn simultaneously from a catheter inserted into the left suprarenal vein to determine the renal extraction coefficient of inulin (CEIN). In addition, renal blood flow (RBF) was continuously measured with an electromagnetic flow transducer fitted around the left renal artery to estimate renal plasma flow (RPF). GFR (GFRCE) was then calculated as the product of RPF and CEIN. To study the effects of ANP on GFR, rats were injected i.v. with 10 microliters of saline without (n = 6; vehicle) or with 1 microgram ANP (n = 6; ANP) and GFRCE and GFRCL were compared before and after each treatment. They did not differ significantly during baseline measurements in each experimental group and were not modified after vehicle. Similarly, RBF remained constant. In contrast, RBF and GFRCE increased rapidly and simultaneously 90 s after ANP, from 9.07 +/- 0.25 to 10.07 +/- 0.35 (12%) and from 1.209 +/- 0.188 to 1.715 +/- 0.190 ml min-1 (42%), respectively (P < 0.05). GFRCL increased to an even greater extent (88%). Moreover, the peak enhancement of GFRCL was delayed and occurred 180 s after ANP. The renal clearance of inulin was thus unduly elevated due to sudden changes in the dead space induced by the diuretic effect of ANP. In conclusion, determination of glomerular filtration rate by the method of renal extraction of inulin provided more reliable results than those achieved using the classical method of renal clearance of inulin. Moreover, it was sufficiently sensitive to detect small and transient changes in GFR induced by the injection of 1 microgram ANP. (+info)
Salt-sensitive hypertension in ANP knockout mice is prevented by AT1 receptor antagonist losartan.
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Mice harboring a functional deletion of the pro-atrial natriuretic peptide (ANP) gene (-/-) develop salt-sensitive hypertension relative to their wild-type (+/+) counterparts after prolonged (>1 wk) maintenance on high-salt (HS, 8% NaCl) diet. We reported recently that the sensitization of arterial blood pressure (ABP) to dietary salt in the -/- mice is associated with failure to downregulate plasma renin activity. To further characterize the role and mechanism of ANG II in the sensitization of ABP to salt in the ANP "knockout" mice, we measured ABP, heart rate (HR), and plasma catecholamine and aldosterone concentrations in -/- and +/+ mice maintained on HS for 4 wk and treated with daily injections of AT1 receptor antagonist DuP-753 (losartan) or distilled water (control). Daily food and water intake and fluid and electrolyte excretion were also measured during the first and last weeks of the dietary regimen. Cumulative urinary excretion of fluid and electrolytes did not differ significantly between genotypes and was not altered by chronic treatment with losartan. Basal ABP and HR were significantly elevated in control -/- mice compared with control +/+ mice. Losartan did not affect ABP or HR in +/+ mice, but reduced ABP and HR in the -/- mice to the levels in the +/+ mice. Total plasma catecholamine was elevated by approximately ten-fold in control -/- mice compared with control +/+ mice. Losartan reduced plasma catecholamine concentration significantly in -/- mice and abrogated the difference in plasma catecholamine between -/- and +/+ mice on HS diet. Plasma aldosterone did not differ significantly between genotypes and was not altered by losartan. We conclude that salt sensitivity of ABP in ANP knockout mice is mediated, at least in part, by a synergistic interaction between ANG II and sympathetic nerve activity. (+info)
Urinary excretion of urodilatin is increased during pressure natriuresis in the isolated perfused rat kidney.
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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)
Differentially-altered vascular guanylate cyclase isoforms in experimental hypertensive rats.
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Pathophysiological implications of the vascular nitric oxide (NO)/cGMP pathway were investigated in various rat models of hypertension. The expression of brain and endothelial constitutive NO synthases (bNOS, ecNOS) was determined by Western blot analysis, and the biochemical activity of soluble and particulate guanylate cyclases (GC) was assessed by the amount of cGMP generated in the thoracic aortae of rats with deoxycorticosterone acetate (DOCA)-salt, two-kidney, one dip (2K1C), and spontaneous hypertension (SHR). Plasma nitrite/ nitrate levels were decreased in DOCA-salt and 2K1C hypertension, and increased in SHR. The vascular expression of bNOS as well as that of ecNOS was decreased along with tissue nitrite/nitrate contents in DOCA-salt and 2K1C hypertension. The expression of both bNOS and ecNOS was increased in SHR with concomitant changes of tissue nitrite/nitrate contents. The activity of soluble GC was decreased, and that of particulate GC was increased in DOCA-salt hypertension. The soluble GC activity was increased, while the particulate GC activity was not affected in 2K1C hypertension. The soluble GC activity was not significantly changed, but the particulate GC activity was decreased in SHR. These results indicate that the high blood pressure is associated with differentially-altered vascular NO/cGMP pathway in different models of hypertension. (+info)
Natriuretic peptides in patients with diastolic dysfunction due to idiopathic dilated cardiomyopathy.
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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.
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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)
Effects of C-type natriuretic peptide on rat cardiac contractility.
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1. Natriuretic peptide receptors have been found in different heart preparations. However, the role of natriuretic peptides in the regulation of cardiac contractility remains largely elusive and was, therefore, studied here. 2. The rate of relaxation of electrically stimulated, isolated rat papillary muscles was enhanced (114.4+/-1. 4%, P<0.01) after addition of C-type natriuretic peptide (CNP; 1 microM). Time to peak tension decreased in parallel (88+/-3 and 75+/-2 msec before and 5 min after addition of CNP, respectively, P<0.01). On the other hand, the rate of contraction slowly decreased when CNP was added to the papillary muscles. These results show that CNP displays a positive lusitropic effect associated with a negative inotropic effect. The effects of CNP were mimicked by 8-bromo-guanosine 3',5' cyclic monophosphate. 3. Addition of CNP to isolated adult rat cardiomyocytes, induced a 25 fold increase in guanosine 3',5' cyclic monophosphate (cGMP) levels and stimulated the phosphorylation of phospholamban and troponin I, two proteins involved in the regulation of cardiac contractility. The levels of adenosine 3',5' cyclic monophosphate (cAMP) were not affected by the addition of CNP to the myocytes. The CNP-dependent phospholamban phosphorylation was accompanied by the activation of the sarcoplasmic reticulum Ca2+-ATPase. 4. In summary, CNP exerts a positive lusitropic effect, in rat papillary muscles. The putative mechanism involved in the lusitropism induced by this peptide, a cGMP-dependent enhancement of the rate of relaxation with a slowly developing negative inotropic effect, seems different to that described for catecholamines. (+info)