Angiotensin II attenuates reflex decrease in heart rate and sympathetic activity in man

Circulatory variables and hormone concentrations in arterial plasma were measured in six normal subjects during angiotensin II (ANG II) step-up infusion of 0.25 and 1.00 ng kg-1 X min. During the 1.00 ng kg-1 X min infusion ANG II plasma concentrations increased from 11 +/- 2 to 48 +/- 6 pg ml-1; i.e., similar to those obtained during acute hypotensive hypovolaemia in man. Mean arterial pressure increased (P less than 0.05) from a resting value of 89 +/- 3 to 97 +/- 5 mmHg. Heart rate and catecholamine concentrations did not change. Plasma aldosterone increased (P less than 0.05) from 36 +/- 4 to 77 +/- 10 pg ml-1 during the infusion. Plasma concentrations of vasopressin, adrenalin and pancreatic polypeptide did not change during the investigation. During the 0.25 and 1.00 ng kg-1 X min infusion subcutaneous blood flow decreased (P = 0.06) to 67 +/- 20 and 66 +/- 26%, respectively, of control. It is concluded that: (1) ANG II in physiological doses in man may augment the sympathetic activity on the circulatory system since compensatory decreases in heart rate or in plasma catecholamines were not observed during the increased arterial pressure; (2) ANG II does not induce a general decrease in vagal tone as plasma pancreatic polypeptide concentrations were unchanged; (3) the obtained plasma concentrations of ANG II do not stimulate the release of vasopressin to plasma; and (4) the threshold for reducing the subcutaneous blood flow is reached within relatively small increments in plasma ANG II.     

Effects, release and disposal of endothelin-1 in conscious dogs.

Cardiovascular and renal responses to a step-up infusion of endothelin-1 (ET-1) (1, 5, and 15 ng kg-1 min-1) were investigated in conscious dogs. In addition, the disappearance of ET-1 in arterial and central venous plasma after an infusion of 10 ng kg-1 min-1 was quantified, and the effects of vasopressin (AVP, 10 ng kg-1 min-1) and angiotensin II (AII, 2, 5, and 10 ng kg-1 min-1) on plasma ET-1 were investigated. The step-up infusion of ET-1 increased the plasma level from 3.6 +/- 0.3 to 243 +/- 23 pg ml-1. Concomitantly, arterial blood pressure increased and heart rate (HR) decreased dose-dependently. Diuresis, sodium, and potassium excretion did not change significantly. However, free water clearance increased during the infusion. Clearance of creatinine and excretion of urea decreased (39 +/- 4 to 29 +/- 3 ml min-1 and 87 +/- 16 to 71 +/- 14 mumol min-1, respectively). Decay curves for ET-1 in venous and arterial plasma were identical, and initial t1/2 was 1.1 +/- 0.1 min. Vasopressin increased arterial blood pressure (107 +/- 4 to 136 +/- 3 mmHg) beyond the infusion period and increased plasma ET-1 (85%). An equipressor dose of AII tended to decrease plasma ET-1. It is concluded that the lung is apparently not important in the removal of ET-1, that the disappearance of ET-1 follows a complex pattern, and vasopressin--in contrast to angiotensin II--is able to increase the plasma concentration of ET-1.(ABSTRACT TRUNCATED AT 250 WORDS)     

Cardiovascular and renal effects of intracerebroventricular angiotensin II in conscious sheep.

Effects on systemic and pulmonary haemodynamics, renal electrolyte excretion, and plasma concentration of vasopressin, catecholamines, electrolytes and proteins in response to intracerebroventricular infusions of [Val5]-angiotensin II (ANG II) at 1, 2 and 4 pmol kg-1 min-1 in isotonic saline for 30 min were studied in conscious sheep (n = 6). Vehicle control infusions were performed in four of the animals. All three doses of ANG II were expected to increase CFS concentration of the peptide above physiological levels. All ANG II infusions were noticed to be dipsogenic, but the animals were not allowed to drink freely until at the end of the experiments (at 120 min post-infusion). The systemic arterial blood pressure increased significantly only in response to 2 and 4 pmol kg-1 min-1, concomitant with an increase of the systemic vascular resistance, whereas the cardiac output and heart rate remained unchanged. The central venous pressure increased only after administration of the highest ANG II dose, while pulmonary artery, and capillary wedge pressures were unaffected during all experiments. The plasma protein and K concentration fell in response to ANG II administration. Also here, the effects were significant only at 2 and 4 pmol kg-1 min-1. The plasma levels of vasopressin, noradrenaline, adrenaline and dopamine did not change significantly in response to any of the infusions. The renal Na excretion increased by 100-400%, but not in a strictly dose-dependent manner. Much smaller and more variable effects were seen on the renal K excretion.(ABSTRACT TRUNCATED AT 250 WORDS)     

Analysis of the actions of angiotensin on the central nervous system of conscious dogs

Angiotensin II (ANG II) acts on the brain to elevate blood pressure (BP), stimulate drinking, increase the secretion of vasopressin and corticotropin (ACTH), and inhibit the secretion of renin. The present studies were designed to evaluate the possible physiological significance of these effects. The experiments were performed in conscious dogs with small catheters chronically implanted in both carotid and both vertebral arteries. ANG II was infused into both carotid or both vertebral arteries in doses of 0.1, 0.33, 1.0, and 2.5 ng.kg-1.min-1. Intravertebral ANG II produced dose-related increases in BP that were generally accompanied by increases in heart rate. Intracarotid angiotensin also increased BP but did not change heart rate. Intracarotid ANG II stimulated drinking and, at the highest dose only, increased the secretion of vasopressin, ACTH, and corticosteroids. Intravertebral and intracarotid ANG II suppressed plasma renin activity (PRA). In a parallel series of experiments, the effects of intravenous ANG II, in doses of 2, 5, 10, and 20 ng.kg-1.min-1, were studied. These infusions produced dose-related increases in BP and water intake and suppressed PRA. Only the highest dose of ANG II increased vasopressin or corticosteroid secretion. Analysis of these results in terms of calculated or measured changes in plasma ANG II concentration indicate that the central cardiovascular and dipsogenic actions of angiotensin, as well as the suppression of PRA, can be elicited by concentrations of the peptide that are within the physiological range. On the other hand high, probably supraphysiological, levels of ANG II are required to increase vasopressin or ACTH secretion.     

Angiotensin causes vasoconstriction during hemorrhage in baroreceptor-denervated dogs

The participation of angiotensin II (ANG II) in the maintenance of arterial blood pressure during hypotensive hemorrhage was examined in unanesthetized, baroreceptor-denervated dogs. When mean aortic blood pressure was reduced to 69.0 +/- 2.2 mmHg, plasma renin activity increased from 0.6 +/- 0.3 ng ANG I X ml-1 X h-1 during the prehemorrhage control period to 4.5 +/- 1.6. Twenty minutes after the hemorrhage, mean aortic blood pressure rose to 78.9 +/- 3.1 mmHg. Subsequent infusion of the angiotensin II antagonist saralasin (5.2-14.0 micrograms X kg-1 X min-1) decreased mean aortic pressure to 59.6 +/- 3.3 mmHg. When 5% dextrose was infused in place of saralasin, mean aortic pressure was 79.3 +/- 4.3 mmHg. The lower aortic blood pressure caused by saralasin infusion was the result of a significant decrease in total peripheral resistance. Resistance was 10.3 +/- 3.2 mmHg X l-1 X min lower during saralasin infusion than during dextrose infusion. We conclude that baroreceptor reflexes are not essential for the elevation of plasma renin activity during hemorrhage. In baroreceptor-denervated dogs subjected to hypotensive hemorrhage, the increased formation of ANG II has a vasoconstrictor action that contributes to the maintenance of arterial blood pressure.     

Effect of hypertonic intracarotid infusions on plasma vasopressin concentration

The effect of short-term bilateral intracarotid infusions of hypertonic saline on plasma vasopressin concentration (pAVP) was evaluated in five dogs. Intracarotid infusion of saline at 90 mumol . kg-1 . min-1 . artery-1 significantly (P less than 0.05) increased jugular vein osmolality (pOsm) and sodium concentration (pNa+) within 2 min. Saphenous vein pOsm was not altered during the 6 min of infusion, whereas pNa+ was increased (P less than 0.05) from 0.8 +/- 0.1 to 2.3 +/- 0.3 pg/ml. Subsequent experiments using hypertonic saline infusions of 90 and 180 mumol . kg-1 . min-1 administered intracarotidly and intravenously for 6 min were performed. Intracarotid isotonic infusions and intravenous hypertonic infusions did not significantly alter pAVP. Hypertonic intracarotid saline increased jugular vein pOsm and pNa+ in a dose-related fashion, whereas saphenous vein pOsm and pNa+ were not significantly changed after 6 min of infusion. Plasma vasopressin, compared with the isotonic intracarotid infusion (1.5 +/- 0.3 pg/ml), was increased (P less than 0.05) after hypertonic saline to 3.2 +/- 0.6 and 4.8 +/- 0.2 pg/ml for the 90 and 180 mumol . kg-1 . min-1 infusions, respectively. The cerebral osmolality indicated by jugular vein pOsm was therefore increased in the absence of changes in systemic pOsm during intracarotid hypertonic infusions. The increase in pAVP in response to these changes in pOsm supports the presence of central osmoreceptors regulating vasopressin release in the area of distribution of the common carotid arteries.     

Effects of losartan, prazosin and a vasopressin V1-receptor antagonist on renal and femoral blood flow in conscious sheep

The regulation of blood flow to different organs is determined by the autonomic nervous system and systemic and/or local vasoactive substances. Although the cardiovascular effects of the renin-angiotensin system (RAS), the sympathoadrenal system and vasopressin (AVP) have been thoroughly studied, there are relatively few investigations on these systems with concomitant measurements of systemic haemodynamics and regional blood flow in conscious unstressed individuals. We therefore studied effects of pharmacological blockade of AVP V1-, angiotensin II (ANG II) AT1-and adrenergic alpha-receptors on central and regional (renal and femoral blood flow) haemodynamics in adult conscious ewes. Eight adult cross-bred ewes were chronically intrumented with peri-vascular ultrasonic flow probes implanted unilaterally around the renal and the femoral artery. While standing in their habitual environment, systemic and regional haemodynamics were measured before and after the following treatments as single intravenous injections. Animals in group A (n = 6) were given isotonic saline (NaCl) followed by the AT1-receptor blocker losartan (LOS, 10 mg kg-1) 30 min later; group B (n = 6) animals were given the alpha-adrenoceptor blocker prazosin (PRAZ, 0.2 mg kg-1); and group C (n = 6) the vasopressin V1 receptor antagonist [d(CH2)5Tyr(Me)AVP] (AVP-a, 10 microg kg-1). PRAZ reduced mean arterial pressure (MAP) by 11% concomitant with an increase in heart rate (HR) (32%), whereas the other substances where without effect on those variables. Femoral blood flow (FBF) was enhanced (increased by 82%) by injection of PRAZ only. Administration of LOS increased the renal blood flow (RBF) by 11% while the other drugs were without effect on that parameter. We conclude that basal renal vascular tone in conscious unstressed sheep is dependent on angiotensinergic mechanism and that blockade of this influence causes a local increase in flow without concomitant effects on systemic haemodynamics.     

Renal response to captopril in conscious dogs pretreated with indomethacin

This study was designed to determine whether the prostaglandins mediate the renal effects of captopril in the conscious sodium-replete dog. In a group of control animals (n = 9), effective renal plasma flow (ERPF) increased from 185 +/- 15 to 230 +/- 12 ml/min and plasma renin activity (PRA) increased from 0.64 +/- 0.15 to 12.9 +/- 1.1 ng ANG I . ml-1 . h-1 after captopril (10 mg/kg bolus plus 10 micrograms . kg-1 . min-1 i.v.) administration. Glomerular filtration rate (GRF) and sodium excretion (UnaV) were also increased significantly following captopril treatment, whereas urine volume (V), potassium excretion (UkV), mean arterial pressure (MAP), and heart rate (HR) remained unchanged throughout the experiment. When the same dose of captopril was given to indomethacin-pretreated dogs (5 mg/kg bolus plus 2 micrograms . kg-1 . min-1 i.v.), ERPF increased from 170 +/- 8 to 265 +/- 18 ml/min and PRA increased from 1.2 +/- 0.4 to 14.6 +/- 3.0 ng ANG I . ml-1 . h-1 after the captopril, while UnaV, UkV, and V remained unchanged. These data demonstrate that the prostaglandins do not mediate the ability of captopril to increase PRA or effective renal plasma flow in this experimental model.     

Cardiovascular effects of parathyroid hormone in conscious sheep

The cardiovascular effects of the synthetic amino terminal fragment of parathyroid hormone, PTH(1-34), were studied in intact conscious sheep. Physiological doses of bovine (b) PTH(1-34), 0.188, 0.376, 0.56 and 0.75 micrograms kg-1 h-1 were infused in random order into conscious sheep for periods of 1 h each. Isotonic saline was infused as a control. Mean arterial blood pressure (MABP) decreased from 99.2 +/- 1.2 mmHg during the control infusion to 88.9 +/- 1.4 mmHg during infusion of the highest dose of PTH. Heart rate (HR) increased from 81.6 +/- 7.3 beats min-1 during the control infusion to 142.3 +/- 14.0 beats min-1 at the highest PTH dose and plasma renin activity (PRA) increased from 0.33 +/- 0.15 ng ml-1 h-1 to 1.54 +/- 0.46 ng ml-1 h-1. Cardiac output (CO), calculated by an indirect method, increased to 176 +/- 28% of the control values. The changes in all four parameters were dose dependent. Renal blood flow (RBF) increased during the PTH infusion period.     

Central venous pressure and plasma arginine vasopressin in man during water immersion combined with changes in blood volume

Summary To investigate the influence of central venous pressure (CVP) changes on plasma arginine vasopressin (pAVP), 8 normal male subjects were studied twice before, during and after immersion to the neck in water at 35.1±0.1 C (mean±SE) for 6 h. After 2 h of immersion, blood volume was either expanded (WI_EXP) by intravenous infusion of 2.01 of isotonic saline during 2 h or reduced by loss of 0.51 of blood during 30 min (WI_HEM). The two studies were randomised between subjects. WI_EXP increased CVP, systolic arterial pressure (SAP), diuresis, natriuresis, kaliuresis and osmolar clearance compared to WI_HEM while haematocrit, haemoglobin concentration and urine osmolality decreased. Heart rate, mean arterial (MAP) and diastolic arterial pressure, plasma osmolality, plasma sodium, plasma potassium and free water clearance did not differ significantly in the two studies. pAVP was significantly higher after 6 h in WI_HEM than after 6 h in WI_EXP (2.0±0.2 vs. 1.6±0.2 pg · ml^–1, mean±SE;P<0.05). pAVP values were corrected for changes in plasma volume due to infusion in order properly to reflect AVP secretion. In conclusion, there was a weak, but significant, negative correlation between CVP and pAVP during the two studies, while during recovery from WI_HEM and WI_EXP decrements in SAP and MAP correlated significantly and strongly with increases in pAVP. It is therefore concluded that it is the arterial baroreceptors rather than the cardiopulmonary mechanoreceptors which are of importance in AVP regulation in man.This investigation was supported by the Danish Space Board, grant no. 1112-32/83, 1112-33/83 and 1112-19/84     

Central transmural venous pressure and plasma arginine vasopressin during negative pressure breathing in man

Summary After overnight food and fluid restriction, 8 normal healthy males were examined in the upright sitting position before (prestudy), during and after (recovery) negative pressure breathing (NPB) with a pressure (P=difference between airway pressure and barometric pressure) of –9.6±0.5 to –10.4±0.4 mm Hg for 30 min. Plasma arginine vasopressin (pAVP) did not change significantly comparing prestudy with 10 and 30 min of NPB or comparing recovery with NPB at 10, 20 or 30 min. However, at 20 min of NBP, pAVP was slightly lower than at prestudy (p<0.05). Central venous pressure (CVP) decreased significantly during NPB, and central transmural venous pressure (CVP—P) increased significantly from –0.9±0.8 mm Hg to 3.8±0.7, 4.3±0.7 and 4.5±0.6 mm Hg (p<0.001) after 10, 20 and 30 min, respectively. Systolic, diastolic and mean arterial pressure and heart rate did not change significantly during NPB. Diuresis, natriuresis, kaliuresis, osmotic excretion and clearance were slightly increased during the recovery hour after NPB compared to prestudy, while urine osmolality decreased during NPB (n=6). However, none of these changes were significant. There was no significant correlation between CVP—P and pAVP. In conclusion, –10 mm Hg NPB for 30 min in upright sitting subjects did not change pAVP consistently, while CVP—P was significantly increased and HR and arterial pressures were unchanged. This lends support to the concept that arterial baroreceptors and not cardiopulmonary mechanoreceptors are of importance in regulating AVP secretion in man.This investigation was supported by the Danish Space Board grant no. 1112-13/84, 1112-19/84, 1112-33/84, and 1112-34/84     

Repeated hypotension induced by nitroprusside and haemorrhage in sheep: effects on vasopressin release and recovery of arterial blood pressure

The arginine vasopressin (AVP) release in response to repeated hypotension caused by intravenous (i.v.) infusion of sodium nitroprusside (SNP) or haemorrhage was studied in conscious euhydrated sheep. Parallel determinations of renal excretion and plasma concentration of AVP were made in experiments involving two consecutive 10-min i.v. infusions of SNP (about 35 micrograms kg-1 min-1) with a 3-h interval between and repeated the next day. The AVP response to the second SNP administration was significantly reduced, but partial recovery was observed in response to the initial infusion the next day. Maximal fall in mean arterial blood pressure (MABP) and its recovery pattern did not differ in response to any of the four SNP infusions. In contrast, impaired recovery of the MABP together with markedly reduced AVP response was seen as a consequence of a hypotensive haemorrhage repeated after 3 h, but not when the interval between haemorrhages was extended to 24 h. The haemorrhage-induced increase in plasma renin activity was not affected by variations in the interval between experiments. It is concluded that the massive AVP liberation normally seen as an effect of acute isovolaemic hypotension becomes markedly reduced upon a renewed fall in the MABP occurring within 3 h. An iteration of hypotensive haemorrhage accentuates this fatigue of the hormonal response, which may contribute to the impaired recovery of the MABP.     

Role of calcium in osmotic and nonosmotic release of vasopressin from rat organ culture

In the present study the role of calcium (Ca) in the stimulation of arginine vasopressin (AVP) release from the cultured rat hypothalamoneurohypophyseal complex (HNC) was examined in response to three different stimuli, 56 mM potassium chloride, an increase in medium osmolality from 290 to 310 mosmol/kg H2O, or 1 X 10(-6) M angiotensin II (ANG II). With all three stimuli AVP release from rat HNC explants was enhanced by increasing Ca concentration in the medium from 0 to 1.8 mM Ca. However, high concentrations of Ca (8 mM) inhibited the response of AVP release to either hyperosmolality or angiotensin II. Chemically dissimilar blockers of cellular Ca uptake, verapamil (5.2 X 10(-6) or 5.2 X 10(-5) M) or nifedipine (5.8 X 10(-6) or 5.8 X 10(-5) M), completely abolished AVP release from rat HNC explants in response to the three different stimuli in 1.8 mM Ca. In a normal concentration of medium Ca (1.8 mM) a Ca ionophore, A23187 (3.8 X 10(-5) M), significantly enhanced the osmotic and nonosmotic (ANG II-stimulated) release of AVP from rat HNC explants compared with controls without Ca ionophore. This effect of Ca ionophore to enhance AVP release was more evident in a lower Ca medium (0.9 mM Ca in the hyperosmolality study and 0.3 mM Ca in the ANG II study). These results therefore indicate that cellular Ca uptake is an important modulator of osmotic and nonosmotic AVP release from the intact rat hypothalamoneurohypophyseal system. The influence of extracellular Ca on the osmotic and nonosmotic release of AVP is also demonstrated.     

Effects on renal sodium and potassium excretion of vasopressin and oxytocin in conscious dogs.

Renal effects of arginine vasopressin and oxytocin were studied in conscious dogs, made water-diuretic by a waterload equivalent to 2% of body weight. Body water and content of sodium were maintained by separate servo-controlled infusions. Peptides were infused for 60 min at rates of 50 pg kg-1 min-1 (arginine vasopressin) or 1 ng kg-1 min-1 (oxytocin), either separately or combined. Infusions increased plasma arginine vasopressin to 1.9 +/- 0.2 (arginine vasopressin alone) and 1.8 +/- 0.3 pg kg-1 (arginine vasopressin plus oxytocin and plasma oxytocin to 72 +/- 5 (oxytocin alone) and 77 +/- 8 pg ml-1 (oxytocin plus arginine vasopressin). Arginine vasopressin or arginine vasopressin plus oxytocin increased urine osmolality similarly by a factor of 13, decreased urine flow to between 5 and 7% of control and decreased free water clearance. Oxytocin reduced urine flow and free water clearance and increased urine osmolality by a factor of 2. Oxytocin and arginine vasopressin separately increased excretion of sodium from 4 +/- 2 to 15 +/- 6 mumol min-1 and from 7 +/- 4 to 25 +/- 13 mumol min-1, respectively. Arginine vasopressin plus oxytocin led to a pronounced natriuresis (13 +/- 4 to 101 +/- 27 mumol min-1). Arginine vasopressin and arginine vasopressin plus oxytocin increased the excretion of potassium by a factor of 2.5. Oxytocin and arginine vasopressin plus oxytocin increased urinary Na+/K+ ratio by a factor of 3.7.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of receptor blockade on metabolism and renal actions of vasopressin in conscious dogs

Vasopressin – but not the V₂ receptor agonist [deamino-cis1,D-Arg8]-vasopressin (dDAVP) – may mediate natriuresis in dogs. The present study investigated this phenomenon by use of nonpeptide antagonists to V_1a and V₂ receptors 1-{1-[4- (3-acetylaminopropoxy)benzoyl]-4-piperidyl}-3,4-dihydro-2 (1H)-quinolinone (OPC-21268) and 5-dimethylamino-1-{4- (2-methylbenzoylamino)-benzoyl}-2,3,4,5-tetrahydro-1H-benzazepine (OPC-31260), respectively) hypothesising that only V_1a inhibition would reduce the natriuresis. In conscious dogs vasopressin secretion was suppressed by water loading (2% body weight) and replaced by infusion of vasopressin (50 pg min^?1 kg^?1) resulting in physiological plasma concentrations (plasma levels of AVP (pAVP) = 2.0 ± 0.1 pg mL^?1). In this setting, OPC-21268 did not change the rate of sodium excretion. OPC-31260 increased water excretion 12-fold without significant changes in sodium excretion. Heart rate, mean arterial blood pressure, glomerular filtration rate, and clearance of endogenous Li⁺ were unchanged. During vasopressin infusion, both antagonists increased pAVP, OPC-21268 by 20% and OPC-31260 by 100% (2.0 ± 0.2–4.0 ± 0.3 pg mL^?1). In the absence of vasopressin infusion, OPC-31260 did not increase pAVP. Thus, the increase in pAVP appeared to be due to a decrease in metabolic clearance rate. The results indicate that the present dose of V_1a receptor inhibitor OPC-21268 does not reduce sodium excretion and that both vasopressin antagonists inhibit vasopressin metabolism.     

Influence of neurohumoral blockade on heart rate and blood pressure responses to haemorrhage in isoflurane anaesthetized rats

Four groups of Sprague-Dawley rats were anaesthetized with isoflurane (ISO) (1.7% end-tidal concentration) in 40% oxygen, and mechanically ventilated. The animals were bled 15 mL kg-1 b.w. from the femoral vein over 10 min, followed by an observation period of 30 min. Ten minutes before haemorrhage each group of animals was pre-treated with intravenous injection/infusion of either: isotonic saline (Group B; CON; n=7), vasopressin V1-receptor antagonist [d(CH2)5Tyr(Me)AVP; 10 microg kg-1] (Group C; AVP-a; n=7), the non-selective angiotensin II receptor antagonist saralasin (10 microg kg-1 min-1) (Group D; SAR; n=7) or hexamethonium (10 mg kg-1) (Group E; HEX; n=7). A separate group of conscious animals were pre-treated with isotonic NaCl and subjected to the same haemorrhage protocol (Group A; AW; n=7). Mean arterial pressure (MAP), heart rate (HR) and blood gases were observed during the experiments. Only pre-treatment with SAR and HEX reduced MAP significantly. The pre-haemorrhage HR was only affected by HEX, which caused a reduction by 17%. The HR was significantly lower at the end of haemorrhage compared with pre-haemorrhage levels in all groups except that group treated with HEX. In that group the HR changed in the opposite direction. The ability to maintain MAP during haemorrhage, and the post-haemorrhage period, was significantly impaired in the groups treated with AVP-a, SAR or HEX compared with the group receiving NaCl. It is concluded that autonomic nervous activity is of major importance for the maintenance of MAP during isoflurane anaesthesia, whereas circulating angiotensin II and vasopressin levels contribute to a much smaller degree in this regard. General anaesthesia in combination with different degrees of neurohumoral blockade impairs the haemodynamic responses to blood loss, seen in conscious individuals. The impairment involves both the early and late phases during haemorrhage, as well as the post-bleeding recovery period. All three neurohumoral systems (autonomic nervous activity, angiotensin II and vasopressin) are of importance for regulating MAP during and after haemorrhage, although the autonomic nervous outflow appears to contribute to a larger extent.     

Age-dependent effects of captopril on the arterial baroreflex control of heart rate in conscious lambs

To test the hypothesis that angiotensin (ANG) II modulates the arterial baroreflex control of heart rate (HR) in an age-dependent manner, various parameters governing the arterial baroreflex control of HR were assessed before and after removal of endogenously produced ANG II by administration of the angiotensin-converting enzyme (ACE) inhibitor, captopril, to conscious, chronically instrumented lambs aged approximately 1 week (8 +/- 1 days; n = 8) or approximately 6 weeks (46 +/- 5 days; n = 8). After administration of captopril, systolic, diastolic and mean arterial pressures decreased significantly from control levels and HR increased; however, the effects were greater in 1- than in 6-week-old lambs. In 1-week-old lambs, after administration of captopril, there was also a significant increase in the slope coefficient, a decrease in minimum HR and a decrease in the point of maximum gain. In 6-week-old lambs, there were no effects of captopril on any of the parameters governing the arterial baroreflex. Therefore, we accept our hypothesis and conclude that the role of ANG II in modulating cardiovascular homeostasis appears to be more predominant in the newborn than later in life.     

Osmotic regulation of evaporative water loss and body temperature by intracranial receptors in the heat-stressed cat

The effect on body temperature (Tb) regulation of alterations in the osmotic milieu of the intracranial compartment has been examined by intracerebroventricular (ICV) infusion of water (0.034 ml . min-1) in heat-stressed hydrated and dehydrated cats. At an ambient temperature (Ta) of 38 degrees C, before ICV water infusion, mean Tb (measured in the hypothalamus) of normally hydrated cats was 38.8 +/- 0.1 degree C and mean evaporative water loss (EWL) was 1.32 +/- 0.18 W . kg-1. ICV water infusion was without significant effect (P greater than 0.05, t-test) on either of these values in normally hydrated animals. In dehydrated animals at Ta 38 degrees C, Tb and EWL were both significantly altered (P less than 0.001) from the normally hydrated state and were measured at 39.9 +/- 0.2 degree C and 0.84 +/- 0.09 W . kg-1 respectively. Infusion of water into dehydrated animals significantly altered pre-infusion levels of Tb and EWL so that Tb fell to 39.4 +/- 0.2 degree C (P less than 0.001) and EWL rose to 1.46 +/- 0.09 W . kg-1 (P less than 0.001). No effect of ICV water infusion on mean plasma vasopressin levels (pAVP) was observed in normally hydrated animals (preinfusion pAVP = 1.3 +/- 0.2 microunit . ml-1, post-infusion pAVP equal 1.3 +/- 0.3 microunit . ml-1, P greater than 0.05). However, a significant reduction in pAVP occurred subsequent to infusion in dehydrated animals (pre-infusion pAVP equal 16.6 +/- 1.85 microunits . ml-1, post-infusion pAVP equal 10.7 +/- 2.3 microunits . ml-1, P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)     

Inhibition of vasopressin and aldosterone release by atrial natriuretic peptide in conscious rabbits.

To elucidate the regulatory role of atrial natriuretic factor (ANF) on vasopressin (AVP) and aldosterone release in conscious rabbits, ANF was administered systematically at a rate of 15 pmol min-1 (kg body wt)-1 for 15 min in two series of experimental animals in which AVP and/or aldosterone production was stimulated. In euhydrated rabbits (series I), systemic administration of angiotensin II (Ang II) (10 pmol min-1 (kg body wt)-1, 15 min) stimulated aldosterone release threefold from basal plasma concentrations (140 pg ml-1). The co-application of ANF inhibited the Ang II-induced release of aldosterone without influencing the non-stimulated AVP system. In dehydrated rabbits (series II) with elevated plasma osmolality and AVP concentration, exogenously applied ANF increased plasma ANF fourfold at marginally reduced arterial pressure. Plasma AVP concentrations were reduced by 3.4 pg ml-1 (25%) on average, and plasma aldosterone concentrations were lowered by 34 pg ml-1 (23%) at unchanged levels of plasma corticosterone. Receptor binding studies using [125I]ANF as radioligand revealed Ang II-independent high-affinity receptors for ANF in the zona glomerulosa of the adrenal gland. With regard to the hypothalamo-neurohypophyseal AVP system, ANF binding sites were localized to the median eminence and neurohypophysis, but not to the magnocellular nuclei. ANF receptors were also labelled in structures lacking a blood-brain barrier such as the subfornical organ and the choroid plexus.     

Role of vasopressin in blood pressure regulation in conscious water-deprived dogs

The role of vasopressin in the regulation of blood pressure during water deprivation was assessed in conscious dogs with two antagonists of the vasoconstrictor activity of vasopressin. In water-replete dogs, vasopressin blockade caused no significant changes in mean arterial pressure, heart rate, plasma renin activity (PRA), or plasma corticosteroid concentration. In the same dogs following 48-h water deprivation, vasopressin blockade increased heart rate from 85 +/- 6 to 134 +/- 15 beats/min (P less than 0.0001), increased cardiac output from 2.0 +/- 0.1 to 3.1 +/- 0.1 1/min (P less than 0.005), and decreased total peripheral resistance from 46.6 +/- 3.1 to 26.9 +/- 3.1 U (P less than 0.001). Plasma renin activity increased from 12.4 +/- 2.2 to 25.9 +/- 3.4 ng ANG I X ml-1 X 3 h-1 (P less than 0.0001) and plasma corticosteroid concentration increased from 3.2 +/- 0.7 to 4.9 +/- 1.2 micrograms/dl (P less than 0.05). Mean arterial pressure did not change significantly. When the same dogs were again deprived of water and pretreated with the beta-adrenoceptor antagonist propranolol, the heart rate and PRA responses to the antagonists were attenuated and mean arterial pressure decreased from 103 +/- 2 to 91 +/- 3 mmHg (P less than 0.001). These data demonstrate that vasopressin plays an important role in blood pressure regulation during water deprivation in conscious dogs.