Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.11.18 (MAP)
 7,412 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In 54 anesthetized rats, the changes in arterial blood pressure, heart rate and/or urine volume, urinary sodium excretion were observed following intracarotid, intrathecal and intracerebroventricular (ICV) injection of atrial natriuretic peptide (ANP). The effects of ANP on the central actions of angiotensin II (AG II) were also examined. The results were as follows: (1) In the cross-circulation preparation of rat head, MAP of the recipient was unchanged and that of the donor was decreased in response to the administration of alpha-hANP (15 micrograms/kg) into the carotid artery of the recipient. (2) By injecting AP III (5 micrograms/kg) intrathecally, MAP, HR and urine volume (V) of the rats (n = 7) showed no change. (3) The ICV injection of AP III (20 micrograms/kg) did not result in changes in MAP, HR, and urinary sodium excretion (UNaV), but there was a transient and significant increase in V. (4) ICV injection of AG II (1 microgram/kg) resulted in an increase of MAP by 1.3 +/- 0.17 kPa (10 +/- 1.3 mmHg, n = 10, P less than 0.001), V by 106% (n = 6, P less than 0.01) and UNaV by 642% (P less than 0.01). (5) ICV injection of AP III 2 min prior to the injection of AG II by the same route, the central hypertensive effect induced by AG II was not affected, while the increments in V and UNaV were decreased significantly (P less than 0.05). The results indicate that (1) ANP is incapable of penetrating the blood-brain barrier owing to its large molecular size and therefore, the central mechanism is not involved in the hypotensive effect induced by intravenous injection of ANF and (2) the central diuretic and natriuretic actions of AG II may be markedly inhibited by ICV injection of ANP, thus indicating the existence of some central antagonistic interactions between AG II and ANP.
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PMID:[Central cardiovascular and renal effects of atrial natriuretic peptide]. 183 84

We studied the hemodynamic changes produced in conscious, chronically instrumented rabbits during steady-state administration of atrial natriuretic peptide (ANP). We administered synthetic alpha-human ANP intravenously (i.v.) at progressively increasing doses of 1, 2, and 4 micrograms/min, each for 30 min. In different experiments in each rabbit, we determined the effects of the peptide under closed-loop conditions in the intact animal and the "direct" circulatory effects of the peptide after "total" blockade of the autonomic nervous system (TAB) and after combined neurohumoral blockade (NHB), where in addition the vascular effects of vasopressin and angiotensin II were also prevented. In intact rabbits, ANP produced a dose-related reduction in mean arterial pressure (MAP, -3 to -14%), which was entirely due to a fall in cardiac output (CO, -14 to -20%), and there was a small rise in total peripheral resistance (TPR 5-12%). Heart rate remained unchanged. In rabbits subjected to TAB and NHB, all hemodynamic effects of ANP were attenuated. There were dose-related falls in left and right atrial pressures which reached maxima of -3.3 +/- 0.9 and -1.8 +/- 0.2 mm Hg, respectively. There was a reversible rise in hematocrit, probably owing to a shift of approximately 8% in blood volume. These effects occurred mainly through direct actions of the peptide, and there was no evidence of systemic vasodilatation. The magnitude of reflex autonomic effects appeared to be less than expected for the observed fall in MAP, suggesting that ANP also inhibited cardiovascular reflexes.
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PMID:Direct and neurohumoral cardiovascular effects of atrial natriuretic peptide. 246 43

In conscious dogs, we examined the hypothesis that the effects of atrial natriuretic peptide (ANP) are mediated by cyclic GMP and tested whether stimulation of the intracellular pathway beyond the ANP receptor level still exerts ANP-like effects during tolerance to ANP in heart failure. We studied the hemodynamic, renal, and hormonal effects of the cyclic GMP analogue 8-bromo-cyclic GMP (8-Br-cyclic GMP) in conscious dogs before and after induction of congestive heart failure by right ventricular pacing. In healthy dogs, 8-Br-cyclic GMP (1-100 micrograms/kg/min) dose-dependently decreased mean arterial pressure (MAP -19% by 100 micrograms/kg/min) and total peripheral resistance (TPR -22%) with no change in cardiac output (CO) and right atrial pressure, increased urine flow (UF 52%), and sodium excretion (UNaV 135%). Plasma renin (62%) and norepinephrine (NE 24%) were increased. In dogs with heart failure, 8-Br-cyclic GMP induced a similar arteriolar dilation (MAP -16%, TPR -23%) with no change in CO and preload. However, the effects on renal excretory function were abolished or markedly attenuated (UF -4%, UNaV 7%). Plasma renin (163%) and aldosterone (40%) were increased. Our findings support the hypothesis that the renal effects of ANP are mediated by cyclic GMP in vivo. The attenuation of renal effects of 8-Br-cyclic GMP in heart failure does not prove but is in agreement with the hypothesis that an intracellular defect beyond cyclic GMP production might be involved in the tolerance to ANP in heart failure.
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PMID:Hemodynamic, renal, and hormonal effects of 8-Br-cyclic GMP in conscious dogs with and without congestive heart failure. 247 97

Several processes participate in the clearance of atrial natriuretic peptide (ANP) from the circulation, one of which is enzymatic degradation. Endoprotease EC 3.4.24.11 (NEP 24.11), present within the kidney in high concentration, has been shown in vitro to degrade ANP. Phosphoramidon and thiorphan, two potent NEP 24.11 inhibitors, have been shown to prevent the enzymatic degradation of ANP. The purpose of the present study was to determine if phosphoramidon or thiorphan would alter the in vivo time course of the pharmacologic effects of ANP. The magnitude and duration of the ANP-induced increase in urine output and sodium and cyclic GMP excretion were examined with and without either thiorphan or phosphoramidon. Six separate groups of anesthetized rats received either a low, medium, or high infusion rate of thiorphan or phosphoramidon. Renal responses to ANP were potentiated and prolonged during the low phosphoramidon infusion (3 Ki) and the medium thiorphan infusion (150 Ki). At high inhibitor infusion rates in the anesthetized rat, ANP elicited a marked depressor response. In the conscious spontaneously hypertensive rat (SHR), a 15-min intravenous (i.v.) infusion of ANP (1 microgram/kg/min) lowered mean arterial pressure (MAP 23 +/- 6 mm Hg), with an approximately 35-min duration of action. A simultaneous i.v. infusion of phosphoramidon (high dose) produced both a potentiation (33 +/- 3 mm Hg) and a prolongation (greater than 65 min to return to baseline) of the depressor response. These data lend support to the hypothesis that enzymatic breakdown of ANP may play an important role in regulating the actions of atrial natriuretic peptide.
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PMID:Degradation of atrial natriuretic peptide: pharmacologic effects of protease EC 24.11 inhibition. 247 3

The immature kidney appears to be less responsive to atrial natriuretic peptide (ANP) than the mature kidney. It has been proposed that this difference accounts for the limited ability of the young animal to excrete a sodium load. To delineate the effects of age on the renal response to exogenous ANP, Sprague-Dawley rats were anesthetized for study at 31-32 days of age, 35-41 days of age, and adulthood. Synthetic rat ANP was infused intravenously for 20 min at increasing doses ranging from 0.1 to 0.8 microgram/kg/min, and mean arterial pressure, glomerular filtration rate, plasma ANP concentration, urine flow rate, and urine sodium excretion were measured at each dose. Since cyclic GMP acts as a second messenger for ANP action, urinary cyclic GMP excretion also was measured. Increasing doses of ANP caused a similar decrease in MAP at all ages studied, and increased glomerular filtration rate in adult but not young rats. Increasing the dose of ANP from 0.1 to 0.4 microgram/kg/min caused a greater rise in urine flow and urinary cyclic GMP excretion in adult than young rats, and urine sodium excretion increased more in adults at all doses (p less than 0.05). However, the rise in plasma ANP concentration also was greater in adults than in young rats (p less than 0.05), indicative of greater systemic clearance of ANP in young animals. Increasing levels of plasma ANP concentration were correlated with a greater rise in urine flow in adult than young (31-32 day old) rats (p less than 0.05), but there was no differential effect on urinary cyclic GMP excretion.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Renal effects of atrial natriuretic peptide infusion in young and adult rats. 285 May 23

To assess the effects of cocaine, administered to the ewe, on the secretion of atrial natriuretic peptide (ANP), Plasma Renin Activity (PRA) and hypoxanthine in the fetus we studied 6 chronically cannulated sheep fetuses late in gestation. The ewe was given an intravenous injection of cocaine (2 mg/kg). Maternal and fetal arterial blood samples were withdrawn prior to the injection and at 2, 5, 10, 15, 45 and 60 min after the injection for the measurement of ANP, PRA and hypoxanthine. Fetal arterial blood pressure (MAP), plasma ANP and protein levels increased and pH and pO2 decreased after cocaine was administered to the ewe. Fetal plasma hypoxanthine and PRA did not change. These results suggest that cocaine administration to the ewe is associated with fetal hypertension, hypoxemia and acidemia all of which may serve as stimuli for the secretion of ANP.
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PMID:Intrauterine exposure to cocaine increased plasma ANP (atrial natriuretic peptide) but did not alter hypoxanthine concentrations in the sheep fetus. 772 97

The goal of this study was to test the hypothesis that increasing or decreasing the load on baroreceptors in the right heart influenced the secretion of arginine vasopressin (AVP), adrenocorticotropic hormone (ACTH), and renin during a state of sustained arterial hypotension. The hypothesis was tested in chronically instrumented conscious dogs prepared with inflatable cuffs around the pulmonary artery (PA) and the thoracic inferior vena cava (IVC). In one protocol (n = 5), mean arterial pressure was reduced 10 or 20% below control by constriction of the PA, a maneuver that caused a fall in left atrial pressure (LAP) and an increase in right atrial pressure (RAP). Plasma AVP, ACTH, atrial natriuretic peptide (ANP), and plasma renin activity (PRA) all increased (P < 0.05) in response to constriction of the PA. Reducing RAP to control by constriction of the IVC during maintained constriction of the PA had no effect on MAP, LAP, plasma AVP, ACTH, or PRA, but plasma ANP fell significantly. In a separate protocol (n = 4), constriction of the IVC was used to reduce MAP 10 or 20% below control, and this led to significant decreases in both LAP and RAP and increases in plasma AVP, ACTH, and PRA. RAP was then increased above control by constriction of the PA without altering either MAP or LAP. Raising RAP from a level that was 6.3 +/- 1.3 mmHg below control to 3.5 +/- 1.0 mmHg above control had no effect on plasma AVP, ACTH, or PRA.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of loading right atrial and ventricular receptors on stimulated AVP, ACTH, and renin secretion in awake dogs. 773 89

Continuous pump-driven veno-venous hemofiltration (CVVH) has become an established method for treatment of acute renal failure (ARF). Since severe disturbances of (micro-) circulation are intimately involved in the bad outcome of these patients, the profile of endocrinological regulators of circulation was prospectively and serially measured in patients undergoing pump-driven CVVH (n = 15). 15 patients with similar APACHE II score, but without ARF and without CVVH were also studied. Endothelin-1 (ET-1), atrial natriuretic peptide (ANP), vasopressin, renin, and catecholamine (epinephrine, norepinephrine) plasma levels were measured before start of CVVH (= "baseline") (in the non-CVVH patients: admission to intensive care unit) and during the next 5 days. Various hemodynamic parameters were additionally monitored. MAP, HR, PAP, CI, and right ventricular hemodynamics (RVEF, RVEDV, RVESV) remained almost unchanged in the CVVH patients and were without differences to the non-CVVH group within the entire investigation period. PCWP and RAP were higher in the CVVH patients already at baseline (RAP, 17.8 +/- 4.0 mmHg; PCWP, 22.1 +/- 4.5 mmHg) (p < .02) and remained elevated in the further course of the investigation. Renin plasma level was higher already at baseline in the CVVH patients (907 +/- 184 pg/ml) (p < .05) and further increased during CVVH (to 1453 +/- 186 pg/mL). Vasopressin increased only in the CVVH group (from 3.80 +/- .66 to 11.85 +/- 1.05 pg/mL) (p < .01).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Changes in regulators of circulation in patients undergoing continuous pump-driven veno-venous hemofiltration. 2597 10

Pressor doses of angiotensin II induced haemodilution in goats despite renal fluid losses. This study was undertaken to determine if this response is dose-dependent and correlated to the vasoconstrictor action of angiotensin II. Angiotensin II at the doses 0.025, 0.05 and 0.1 micrograms min-1 was given intravenously to five goats. Mean arterial blood pressure increased by 3, 10 and 20 mmHg, respectively, and the renal Na excretion rose. The haematocrit decreased by 7, 10, and 9% (percentage of control values) and the plasma protein concentration by 1% (n.s.), 4.5, and 3.5%, respectively. Infusions of phenylephrine (40 micrograms min-1; n = 6) caused an equivalent increase of blood pressure and renal Na excretion as angiotensin II (0.1 micrograms min-1), but the haematocrit increased by 16% and the plasma protein concentration by 6.5%. Infusions of atrial natriuretic peptide (1 microgram min-1) alone or together with angiotensin II (0.1 microgram min-1), or phenylephrine were also given (n = 6). Infusions of atrial natriuretic peptide alone did not change blood pressure, but renal Na excretion increased. The haematocrit rose by 10.5% and the plasma protein concentration by 7.6%. Adding atrial natriuretic peptide to the angiotensin II solution attenuated the rise of MAP and counteracted the haemodilution, but did not decrease the natriuresis. Infusions of phenylephrine plus atrial natriuretic peptide caused similar elevations of blood pressure and renal Na excretion as phenylephrine alone. The haematocrit rose by 24% and the plasma protein concentration by 13%. These results show that in the intact conscious goat rapid and marked changes in haematocrit and plasma protein concentration can be provoked by intravenous infusions of vasoactive agents and that these effects are not correlated to changes in arterial blood pressure or renal Na excretion.
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PMID:Discrepant effects of angiotensin II and phenylephrine on plasma volume in conscious goats. 804 38

Changes in hemodynamic and metabolic parameters (systemic oxygen delivery, [DO2], oxygen consumption [VO2], arterial lactate content) in brain-dead and control pigs in the absence of any inotropic or fluid support were studied. Brain death was induced by the inflation of a Foley catheter balloon placed into the subdural space of the animals. Serial atrial natriuretic peptide (ANP) determinations were performed to evaluate concomitant changes occurring in the endocrine function of the heart. Experiments were completed by a volume expansion protocol to provide a dynamic evaluation of these parameters. A significant increase in heart rate (from 113 +/- 5 to 176 +/- 11 beats/min), pulmonary capillary wedge pressure (from 7 +/- 1 to 12 +/- 3 mmHg), dP/dt (from 2040 +/- 340 to 4200 +/- 660 mmHg/sec-1), cardiac output (from 2.4 +/- 0.2 to 3.3 +/- 0.4 L/min), mean arterial pressure (from 66 +/- 8 to 93 +/- 14 mmHg), and systemic oxygen delivery (from 360 +/- 30 to 530 +/- 90 ml/min-1), was observed following brain death induction. These parameters returned below basal values within 60 min. On the contrary, serum lactate and VO2 remained unchanged. Following volume expansion, brain-dead pigs exhibited impaired hemodynamic response, with a significant decrease in dP/dt, MAP, and DO2. These changes were accompanied by a significant decrease in VO2 and a significant increase in lactate plasma levels. At the same time, a similar increase in ANP release was observed in both groups in response to volume expansion, suggesting that despite impaired myocardial contractility, endocrine function of the heart was preserved following brain death. We conclude that brain death leads to early impaired left ventricular contractility, which could be responsible for the changes observed in aerobic to anaerobic metabolism in response to rapid volume infusion. These results suggest that the use of fluid infusion to reduce the need in inotropic support in conventional therapeutic modalities should be used with care in the management of a brain-dead potential organ donor.
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PMID:Changes in hemodynamic and metabolic parameters following induced brain death in the pig. 762 35


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