Comparative bioactivity of atrial, brain, and C-type natriuretic peptides in conscious sheep

1996 ◽  
Vol 270 (6) ◽  
pp. R1324-R1331 ◽  
Author(s):  
C. J. Charles ◽  
E. A. Espiner ◽  
A. M. Richards ◽  
M. G. Nicholls ◽  
T. G. Yandle
Keyword(s):  
Cardiac Output ◽  
Arterial Pressure ◽  
Natriuretic Peptide ◽  
Biological Effects ◽  
Plasma Aldosterone ◽  
Endocrine Function ◽  
Metabolic Clearance ◽  
Functional Homology ◽  
Conscious Sheep ◽  
Species Specific

Although atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) appear to share functional homology, there is doubt concerning a possible endocrine function for C-type natriuretic peptide (CNP) and the relative potency of species-specific forms of these hormones. Accordingly, we have examined the biological effects, interactions, and pharmacokinetics of equimolar doses (0.5 followed by 2.5 pmol.kg-1.min-1, each for 2 h) of species-specific forms of ANP, BNP-26, and CNP-22 in vehicle-controlled studies in normal conscious sheep. Although pharmacokinetics (metabolic clearance rates of 5.7 +/- 1.17, 7.5 +/- 1.36, and 4.7 +/- 0.71 l/min and half-lives of 3.9 +/- 0.42, 2.5 +/- 0.21, and 2.0 +/- 0.18 min for ANP, BNP, and CNP, respectively) are similar, the biological effects and actions on endogenous natriuretic peptide levels differ. Plasma BNP was significantly increased by CNP infusion (P < 0.0001), as was CNP by BNP infusions (P = 0.0009). Compared with ANP and BNP, which were equipotent in stimulating plasma guanosine 3',5'-cyclic monophosphate (cGMP; P < 0.0001 for both) and lowering arterial pressure (P < 0.05 for both) and cardiac output, CNP infusions induced only a small increment in cGMP and had no significant hemodynamic actions. In contrast, all three peptides suppressed plasma aldosterone levels (P < 0.05 for each), yet none induced significant natriuresis. Actions of CNP to increase BNP (and ANP) may account for the observed bioactivity of CNP. The findings show that potentially important interactions occur among all three hormones that need to be considered when interpreting the effects of individual peptides, particularly CNP.

Biological actions and pharmacokinetics of C-type natriuretic peptide in conscious sheep

1995 ◽  
Vol 268 (1) ◽  
pp. R201-R207 ◽  
Author(s):  
C. J. Charles ◽  
E. A. Espiner ◽  
A. M. Richards ◽  
M. G. Nicholls ◽  
T. G. Yandle
Keyword(s):  
Cardiac Output ◽  
Arterial Pressure ◽  
Natriuretic Peptide ◽  
Vascular Tissue ◽  
Controlled Study ◽  
Metabolic Clearance ◽  
Regional Hemodynamics ◽  
Conscious Sheep ◽  
Conscious Animals ◽  
Plasma Half Life

C-type natriuretic peptide (CNP) is found in abundance in neural tissue and in endothelial cells of vascular tissue, where it may participate in the regulation of vascular tone. However, few studies have examined the metabolism and systemic actions of CNP in conscious animals. Accordingly, we investigated the hemodynamic, renal, and hormonal effects of intravenous CNP-22 administered at two doses (1 and 10 pmol.kg-1.min-1 as dose 1 and dose 10, respectively) in a vehicle-controlled study in normal conscious sheep (n = 8). Plasma CNP levels were raised from a mean baseline level of 2-3 pmol/l (detection limit) to plateau at 10 +/- 1.2 and 115 +/- 18 pmol/l during doses 1 and 10, respectively. Metabolic clearance rates were 3.15 +/- 0.39 and 2.48 +/- 0.36 l/min, respectively. The plasma half-life of CNP on termination of infusion was rapid (1.6 +/- 0.27 min). Dose 10 increased plasma guanosine 3',5'-cyclic monophosphate (P = 0.0002), reduced cardiac output by 18% (P = 0.01), but did not significantly affect mean arterial pressure. Similar suppression (15%) of cardiac output occurred during dose 1 (P = 0.078). Both doses were natriuretic. This study demonstrates that CNP is natriuretic in sheep and lowers cardiac output without significantly affecting arterial pressure. CNP may play an important role in the regulation of regional hemodynamics and fluid homeostasis.

Atrial natriuretic peptide increases resistance to venous return in rats

1987 ◽  
Vol 252 (5) ◽  
pp. H894-H899 ◽  
Author(s):  
Y. W. Chien ◽  
E. D. Frohlich ◽  
N. C. Trippodo
Keyword(s):  
Blood Flow ◽  
Cardiac Output ◽  
Arterial Pressure ◽  
Atrial Natriuretic Peptide ◽  
Natriuretic Peptide ◽  
Total Peripheral Resistance ◽  
Venous Return ◽  
Venous Pressure ◽  
Peripheral Resistance ◽  
Atrial Natriuretic

To examine mechanisms by which administration of atrial natriuretic peptide (ANP) decreases venous return, we compared the hemodynamic effects of ANP (0.5 microgram X min-1 X kg-1), furosemide (FU, 10 micrograms X min-1 X kg-1), and hexamethonium (HEX, 0.5 mg X min-1 X kg-1) with those of vehicle (VE) in anesthetized rats. Compared with VE, ANP reduced mean arterial pressure (106 +/- 4 vs. 92 +/- 3 mmHg; P less than 0.05), central venous pressure (0.3 +/- 0.3 vs. -0.7 +/- 0.2 mmHg; P less than 0.01), and cardiac index (215 +/- 12 vs. 174 +/- 10 ml X min-1 X kg-1; P less than 0.05) and increased calculated resistance to venous return (32 +/- 3 vs. 42 +/- 2 mmHg X ml-1 X min X g; P less than 0.01). Mean circulatory filling pressure, distribution of blood flow between splanchnic organs and skeletal muscles, and total peripheral resistance remained unchanged. FU increased urine output similar to that of ANP, yet produced no hemodynamic changes, dissociating diuresis, and decreased cardiac output. HEX lowered arterial pressure through a reduction in total peripheral resistance without altering cardiac output or resistance to venous return. The results confirm previous findings that ANP decreases cardiac output through a reduction in venous return and suggest that this results partly from increased resistance to venous return and not from venodilation or redistribution of blood flow.

Atrial natriuretic peptide correlates with pulmonary arterial pressure and cardiac output

Peptides ◽  
1987 ◽  
Vol 8 (2) ◽  
pp. 285-290 ◽  
Author(s):  
K. Naruse ◽  
M. Naruse ◽  
T. Honda ◽  
K. Obana ◽  
H. Sakurai ◽  
...  
Keyword(s):  
Cardiac Output ◽  
Arterial Pressure ◽  
Atrial Natriuretic Peptide ◽  
Natriuretic Peptide ◽  
Pulmonary Arterial Pressure ◽  
Pulmonary Arterial ◽  
Atrial Natriuretic

scholarly journals C-type natriuretic peptide in reproduction, pregnancy and fetal development

2004 ◽  
Vol 180 (1) ◽  
pp. 17-22 ◽  
Author(s):  
T Walther ◽  
H Stepan
Keyword(s):  
Natriuretic Peptide ◽  
Fetal Development ◽  
De Novo ◽  
Biological Effects ◽  
Endocrine Function ◽  
Comprehensive Overview ◽  
Specific Expression ◽  
Embryonic And Fetal Development ◽  
Organ Specific ◽  
Reproductive Processes

C-type natriuretic peptide (CNP) belongs to the natriuretic peptide family that consists of three structurally related peptides with a 17-amino acid ring linked by a disulfide bond. In contrast to atrial and brain natriuretic peptides that are mainly cardiovascular hormones, CNP acts predominantly in an autocrine/paracrine fashion, is commonly considered to be an endothelial hormone with antimitogenic properties, and is characterized as a regulator of endochondral ossification. Its biological effects are mediated by an intracellular cGMP accumulation via specific membrane-bound guanylyl cyclase B (GC-B) activation. There is growing evidence that this peptide is also involved in various reproductive processes as well as in embryonic and fetal development. In rodents, CNP and its receptor are highly expressed in the uterus and ovaries with specific regulation during the estrous cycle. During pregnancy, CNP mRNA is detectable in mice embryos and shows an organ-specific expression in maternal reproductive tIssues with the highest concentration in the placenta. This could indicate a defined biological function of the CNP/GC-B/cGMP axis in gestation e.g. antagonizing vasoconstrictive peptides like angiotensin II. In humans, besides a postulated fetal de novo synthesis of CNP, both the peptide and its receptor are expressed in the placenta and myometrium with opposite regulation of CNP in pregnancies complicated by pre-eclampsia or intrauterine growth retardation. Since the maternal plasma levels do not reflect these alterations, one can conclude that this part of the natriuretic peptide system acts locally suggesting that CNP-stimulated cGMP release exhibits organ-specific effects. Importantly, CNP has also become a peptide with a distinct role in male reproductive processes, since endocrine function of the testis and the regulation of penile erection are regulated by the CNP/GC-B axis. This review gives a comprehensive overview of the multiple functions of CNP in reproduction and pregnancy as well as in embryonic and fetal development.

INCREASED STEROID METABOLIC CLEARANCE RATE IN ANEPHRIC PATIENTS

1974 ◽  
Vol 75 (4) ◽  
pp. 756-762 ◽  
Author(s):  
P. Corvol ◽  
X. Bertagna ◽  
J. Bedrossian
Keyword(s):  
Cardiac Output ◽  
Clearance Rate ◽  
Plasma Aldosterone ◽  
Normal Male ◽  
Metabolic Clearance ◽  
Metabolic Clearance Rate ◽  
Aldosterone Level ◽  
High Cardiac Output ◽  
Plasma Aldosterone Level ◽  
Anephric Patients

ABSTRACT The control of plasma aldosterone level depends on the secretion rate and on the metabolic clearance rate (MCR) of the hormone. The rate of aldosterone metabolism was measured in 6 anephric patients in comparison with normal volunteers. Unexpected high aldosterone MCR's were found in the anephric patients: 2700 ± 265 1/24 h (M ± sem), as compared to the normals (1600 ± 57). Passive 45° tilting did not significantly change aldosterone MCR's in both the normal and anephric patients. This increase in aldosterone MCR might be explained by a high hepatic plasma flow due to a high cardiac output. The haemodynamic condition of these patients could also explain the high testosterone MCR found in 3 male anephric patients, although testosterone-oestradiol binding globulin was in the high normal male range.

scholarly journals Apelin-13 induces a biphasic haemodynamic response and hormonal activation in normal conscious sheep

2006 ◽  
Vol 189 (3) ◽  
pp. 701-710 ◽  
Author(s):  
Christopher J Charles ◽  
Miriam T Rademaker ◽  
A Mark Richards
Keyword(s):  
Heart Rate ◽  
Cardiac Output ◽  
Arterial Pressure ◽  
Peripheral Resistance ◽  
Right Atrial ◽  
Large Animal Model ◽  
High Dose ◽  
Large Animal ◽  
Plasma Arginine ◽  
Conscious Sheep

Whilst the tissue distribution and range of biological actions reported for apelin suggest a role for the peptide in pressure/volume homeostasis, conflicting reports make the precise role unclear. Furthermore, few integrated studies have been performed and there are no reports of bioactivity of apelin in a large animal model. Accordingly, we have examined the haemodynamic, hormonal and renal effects of apelin in ten normal conscious sheep. Apelin (1 mg i.v. bolus) induced a biphasic haemo-dynamic response characterised by an acute fall in arterial pressure and a rise in heart rate followed immediately by a rise in arterial pressure and a fall in heart rate. The secondary hypertensive phase was associated with a fall in cardiac output (P=0.015) and significant rises in calculated total peripheral resistance (CTPR) (P<0.001) and right atrial pressure (RAP) (P=0.031). Electrocardiogram changes were also observed in four of ten sheep, most notably varying degrees of atrioventricular block. Apelin also induced significant rises in plasma arginine vasopressin (P=0.009), adrenocorticotrophin (P=0.012), aldosterone (P=0.001), cortisol (P=0.014), atrial (P=0.036) and brain (P<0.001) natriuretic peptide, cyclic GMP (P=0.003) and cyclic AMP (P=0.002) levels with no effect on renal indices. In conclusion, high dose administration of apelin to normal conscious sheep induces a significant biphasic response in arterial pressure and heart rate associated with rises in RAP and CTPR and a fall in cardiac output. Apelin also increases circulating levels of a number of vasoactive hormones. Taken together, these results suggest a potential role for apelin in pressure/volume homeostasis.

Beneficial or Detrimental Effects on Hemodynamics Depends on Dose of Dietary Potassium in Rapp Dahl Salt-Sensitive (DS) Rats.

Hypertension ◽  
2000 ◽  
Vol 36 (suppl_1) ◽  
pp. 711-712
Author(s):  
William M Manger ◽  
Shlomoh Simchon ◽  
Kung-Ming Jan ◽  
Francis Haddy ◽  
Charles T Stier ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Cardiac Output ◽  
Mean Arterial Pressure ◽  
Arterial Pressure ◽  
Plasma Aldosterone ◽  
Lower Blood Pressure ◽  
Hemodynamic Effects ◽  
Lower Blood ◽  
Dietary Potassium ◽  
Biphasic Effect

P103 Dietary K supplementation was reported to lower blood pressure and prevent strokes in humans and to prevent strokes in hypertensive DS rats. We report a biphasic effect as a function of KCl dose in DS rats that were fed 1% NaCl with increasing dietary KCl, namely, 0.7, 2.6, 4, and 8%. After 8 months on 1% NaCl supplemented with 0.7% KCl, mean arterial pressure (MAP), plasma volume (PV), cardiac output (CO), total peripheral, renal and cerebral vascular resistances (TPR, RVR, CVR) increased compared to salt-resistant DR rats; on 2.6% KCl all these parameters decreased compared with DS on 0.7% KCl diet. When KCl was increased to 4 and 8%, MAP, PV, CO and RVR progressively increased in DS and DR rats, without changing TPR; these changes were accompanied by parallel increases in plasma aldosterone. Only DS rats on the ”optimal“ 2.6% KCl supplement maintained hemodynamics most similar to control DR rats and thus prevented Na retention, hypertension, increases in RVR and CVR. These beneficial hemodynamic effects may explain stroke prevention.

Hemodynamic, hormonal, and renal effects of adrenomedullin in conscious sheep

1997 ◽  
Vol 272 (6) ◽  
pp. R2040-R2047 ◽  
Author(s):  
C. J. Charles ◽  
M. T. Rademaker ◽  
A. M. Richards ◽  
G. J. Cooper ◽  
D. H. Coy ◽  
...  
Keyword(s):  
Cardiac Output ◽  
Arterial Pressure ◽  
Peripheral Resistance ◽  
Plasma Renin ◽  
Hypotensive Effect ◽  
Right Atrial ◽  
Controlled Study ◽  
Plasma Norepinephrine ◽  
Pressure Lowering ◽  
Conscious Sheep

Adrenomedullin is a recently discovered peptide that has been shown to reduce arterial pressure and induce natriuresis. However, few studies have examined the biological actions of adrenomedullin in conscious animals in an integrative manner. Accordingly, we have examined the hemodynamic, renal, and endocrine actions of adrenomedullin infused intravenously at 10 and 100 ng.kg-1.min-1 (each 90 min) in a vehicle-controlled study in eight normal conscious sheep. Adrenomedullin reduced right atrial pressure (P < 0.05) and diastolic (15 mmHg, P < 0.01) and mean arterial pressure (10 mmHg, P < 0.05) and increased cardiac output (3 l/min, P < 0.001). Total peripheral resistance was reduced 40% (P < 0.001). Urinary sodium was reduced to 35% of control during the 90-min clearance period immediately postinfusion (P < 0.05). Adrenomedullin increased plasma adenosine 3',5'-cyclic monophosphate levels (P < 0.001). Plasma renin activity was elevated during adrenomedullin (P < 0.001) coincident with the peak hypotensive effect, whereas plasma aldosterone was not affected and plasma norepinephrine levels fell (P < 0.05). In conclusion, adrenomedullin had clear blood pressure-lowering effects with increased cardiac output and stimulation of renin but suppressed sympathetic activation in conscious sheep. The physiological implications of these findings require further study.

Comparative actions of adrenomedullin and nitroprusside: interactions with ANG II and norepinephrine

2001 ◽  
Vol 281 (6) ◽  
pp. R1887-R1894 ◽  
Author(s):  
Christopher J. Charles ◽  
M. Gary Nicholls ◽  
Miriam T. Rademaker ◽  
A. Mark Richards
Keyword(s):  
Heart Rate ◽  
Arterial Pressure ◽  
Peripheral Resistance ◽  
Plasma Renin ◽  
Urine Flow ◽  
Plasma Aldosterone ◽  
Ang Ii ◽  
Biological Responses ◽  
Conscious Sheep

The role of adrenomedullin (ADM) in volume and pressure homeostasis remains undefined. Accordingly, we compared the biological responses to infusions of ADM and nitroprusside (NP; matched for reduction of arterial pressure) and assessed their effects on responses to ANG II and norepinephrine in eight conscious sheep. During matched falls in arterial pressure (8–10 mmHg, both P < 0.001) ADM and NP induced similar increases in heart rate. ADM increased cardiac output ( P < 0.001), and the fall in calculated peripheral resistance was greater with ADM than NP ( P = 0.013). ADM infusions raised plasma ADM levels ( P < 0.001), plasma renin activity ( P = 0.001), and ANG II ( P < 0.001) but tended to blunt any concurrent rise in aldosterone compared with NP ( P = 0.056). ADM maintained both urine flow ( P < 0.001) and sodium excretion ( P = 0.01) compared with falls observed with NP. ADM attenuated the vasopressor actions of exogenous ANG II ( P = 0.006) but not norepinephrine. In addition, ADM antagonized the ANG II-induced rise in plasma aldosterone ( P < 0.001). In conclusion, ADM induces a different spectrum of hemodynamic, renal, and endocrine actions to NP. These results clarify mechanisms by which ADM might contribute to volume and pressure homeostasis.

Peripheral circulatory responses to 96 h of hypoxia in conscious sinoaortic-denervated sheep

1986 ◽  
Vol 250 (5) ◽  
pp. R868-R874
Author(s):  
J. A. Krasney ◽  
K. Miki ◽  
K. McAndrews ◽  
G. Hajduczok ◽  
D. Curran-Everett
Keyword(s):  
Heart Rate ◽  
Cardiac Output ◽  
Arterial Pressure ◽  
Coronary Flow ◽  
Systemic Arterial Pressure ◽  
Arterial Pco2 ◽  
Blood Flows ◽  
Pulmonary Arterial ◽  
Conscious Sheep ◽  
Arterial Po2

Conscious sheep exposed to 4 days of eucapnic hypoxia (arterial PO2 40 Torr, arterial PCO2 33 Torr) respond with sustained increases in heart rate, cardiac output, and coronary, cerebral, and respiratory muscle blood flows (Respir. Physiol. 59: 197-211, 1985). In the present investigation, seven adult ewes were studied during similar levels of hypoxia (arterial PO2 40 Torr, 4 days) after chronic section of the carotid sinus and aortic depressor nerves to determine the contribution of the arterial chemoreceptors to these responses. Ventilation and arterial PCO2 did not change, indicating that ventilatory acclimation did not occur. O2 consumption decreased by 24%. Cardiac output (thermodilution) increased by 12% for only 24 h, heart rate increased by 44-69% above normoxic levels for only 72 h, and stroke volume was unchanged. Systemic arterial pressure was unchanged, whereas pulmonary arterial pressure rose by 56%. Coronary flow (radio-labeled microspheres) increased from 155 +/- 50.4 (SE) to 299 +/- 81 ml X min-1 X 100 g-1 at 24 h and then declined to normoxic levels by 96 h. Cerebral flow rose from 62 +/- 6.5 to between 85 +/- 14.4 and 124 +/- 43.5 ml X min-1 X 100 g-1 for 96 h. These results indicate that the arterial chemoreflexes or reflexes secondary to increased ventilation are responsible for the continued elevation of heart rate, cardiac output, and coronary flow during eucapnic hypoxia.

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