Differentiation of the peptidergic vasoregulatory response to standardized splanchnic hypoperfusion by acute hypovolaemia or sepsis in anaesthetized pigs.

This study was performed to integratively investigate the vasoregulatory response during standardized splanchnic hypoperfusion in pigs. Splanchnic perfusion was reduced to 50% of baseline by: haemorrhage by 20 and 40% of the estimated total blood volume; femoral venous infusion of live E. coli to establish sepsis of systemic origin; portal venous infusion of live E. coli to establish sepsis of splanchnic origin. Invasive haemodynamic monitoring and radioimmunoassay analyses of arterial plasma concentrations of angiotensin II, endothelin-1 and atrial natriuretic peptide were carried out. Acute hypovolaemia reduced systemic and splanchnic vascular resistances following transient increases and increased angiotensin II levels (+587%), whereas endothelin-1 and atrial natriuretic peptide levels did not change significantly. Systemic sepsis following femoral venous infusion of E. coli resulted in increased splanchnic vascular resistance and increased levels of angiotensin II (+274%), endothelin-1 (+134%) and atrial natriuretic peptide (+185%). Infusion of E. coli via the portal venous route induced an increase in splanchnic vascular resistance associated with particularly elevated levels of angiotensin II (+1770%) as well as increased endothelin-1 (+201%) and atrial natriuretic peptide (+229%) concentrations. Hypovolaemia and sepsis, although standardized with a predefined level of splanchnic hypoperfusion, elicited differentiated cardiovascular and vasopeptidergic responses. Sepsis, particularly of portal origin, notably increased splanchnic vascular resistance related to increased production of the vasoconstrictors angiotensin II and endothelin-1. The role of atrial natriuretic peptide as a vasodilator seems to be of subordinate importance in hypovolaemia and sepsis.     

Mechanisms of mechanical load-induced atrial natriuretic peptide secretion: role of endothelin, nitric oxide, and angiotensin II

There are three members in the natriuretic peptide hormone family, atrial natriuretic peptide (ANP), B-type natriuretic peptide (BNP, brain natriuretic peptide), and C-type natriuretic peptide (CNP), that are involved in the regulation of blood pressure and fluid homeostasis. CNP is found principally in the central nervous system and vascular endothelial cells while ANP and BNP are cardiac hormones. ANP is synthesized mainly in the atria of the normal adult heart, while BNP is produced by both the atria and ventricles. The mechanisms controlling ANP release have been the subject of intense research, and are now fairly well understood. The major determinant of ANP secretion is myocyte stretch. Although much less is known about the factors regulating BNP release from the heart, myocyte stretch has also been reported to stimulate BNP release from both atria and ventricles. However, whether wall stretch acts directly or via factors such as endothelin-1, nitric oxide, or angiotensin II liberated in response to distension has not been established. Recent studies show that by stimulating endothelin type A receptors endothelin plays an important physiological role as a mediator of acute-volume load-induced ANP secretion from atrial myocytes in conscious animals. In fact, endogenous paracrine/autocrine factors liberated in response to atrial wall stretch rather than direct stretch appears to be responsible for activation of ANP secretion in response to volume load, as evidenced by almost complete blockade of ANP secretion during combined inhibition of endothelin type A/B and angiotensin II receptors. Furthermore, under certain experimental conditions angiotensin II and nitric oxide may also exert a significant modulatory effect on stretch-activated ANP secretion. The molecular mechanisms by which endothelin-1, angiotensin II, and nitric oxide synergistically regulate stretch-activated ANP release are yet unclear.     

Durstregulation bei terminaler Niereninsuffizienz

Summary About 30% of hemodialyzed patients are suffering from chronic fluid overload despite advice to restrict the oral fluid intake. To investigate the cause of the abnormal drinking behaviour a clinical study was performed in 51 non-diabetic patients with endstage renal disease exhibiting lower interdialytic weight gain (<3 kg,n=17) and increased interdialytic weight gain (>3 kg,n=34). Blood pressure, body weight self-estimated thirst intensity before and after hemodialysis were analyzed. Biochemical and behavioral variables were measured including hormonal factors of water and sodium metabolism. Significant differences of dry weight, creatinine, urea nitrogen and thirst intensity were found between the two groups. Catecholamines, renin, angiotensin II, aldosterone, vasopressin and atrial natriuretic peptide exhibited a similar pattern in both groups. Atrial natriuretic peptide decreased during hemodialysis in both groups, angiotensin II, however, and norepinephrine showed an exaggerated response to ultrafiltration rate in polydipsic patients. These results suggest that changes in serum osmolality during hemodialysis did not contribute to thirst and drinking behaviour. It seems that postdialytic hypovolaemia together with higher plasma-angiotensin II-levels is responsible for increased oral intake of fluid and excessive weight gain.

     

Effects of histamine, vasopressin, and angiotensin II on hepatosplanchnic hemodynamics, liver function, and hepatic metabolism in cats.

Continuous i.v. infusions of histamine (5 mug/kg - min), vasopressin (10 mU/kg -min), or angiotensin II (0.5 mug/kg - min) were given to fasting cats. Hepatic arterial flow was decreased 30% by histamine, increased 30% by vasopressin, and not significantly affected by angiotensin, whereas portal venous flow was increased 25% by histamine, decreased 40% by vasopressin, and not significantly affected by angiotensin. The hepatic arterial conductance was decreased about 25% by histamine and angiotensin, and not significantly affected by vasopressin. The gastrointestinal conductance was decreased about 40% by vasopressin and angiotensin, and increased 25% by histamine. The conductance in the intrahepatic low pressure vessels was not affected by histamine and vasopressin, but decreased 25% during the infusion of angiotensin. These hemodynamic effects, however, were not accompanied by changes in the liver function or hepatic metabolism as judged from the splanchnic elimination of ethanol, the hepatic uptake and excretion of ICG, the hepatic oxygen consumption, and lactate and ketone production. This indicates that the functional capacity of the liver and thereby the number of sinusoids perfused is not markedly influenced by these drugs. Vasopressin caused a decrease in the oxygen consumption and an increase in the lactate production in the prehepatic splanchnic area, which may be due to a redistribution of the gastrointestinal blood flow.     

Influence of indomethacin and of prostaglandin E1 on total and regional blood flow in man

The central and regional circulatory effects in man of the prostaglandin synthetase inhibitor indomethacin and of prostaglandin E1 (PGE1) were studied. Systemic blood pressure, cardiac output, and renal and splanchnic blood flow were measured at rest, following infusion of indomethacin (50 mg i.v.), and during infusion of PGE1 (4--8 mg x min-1 i.v.) after the administration of indomethacin. An increase in the total systemic resistance (+ 20%), as well as in the renal (+ 30%) and splanchnic (+ 16%) vascular resistances developed rapidly following the administration of indomethacin. Infusion of PGE1 completely restored the resistance in the renal and splanchnic regions, and in addition markedly increased the blood flow in non-visceral tissues. We suggest that the circulatory effects by indomethacin are elicited via the drug's inhibitory effect on prostaglandin synthetase in the vessel walls, and that vasodilating products of PG synthetase affect the regional blood flow distribution in man.     

Vascular amyloid of unknown origin and senile transthyretin amyloid in the lung and gastrointestinal tract of old age: Histological and immunohistochemical studies

The histological and immunohistochemical characteristics and the incidence of amyloid deposits in the tissues of the lung and gastrointestinal tract were investigated in 64 autopsied individuals who were 80 years and older (age range: 80-92 years; mean: 83.3 years). Immunohistochemical examination was performed with antibodies against amyloid A, transthyretin, immunoglobulin lambda and kappa light chain amyloid fibril proteins, beta2-microglobulin, beta protein, apolipoprotein AI, apolipoprotein AII, atrial natriuretic peptide, apolipoprotein E, and amyloid P component. Transthyretin amyloid fibril protein (ATTR) deposits were observed in five cases (7.8%). Gastrointestinal amyloid deposits of unknown origin were observed in the veins of the gastrointestinal tract in 26 cases (40.6%). This amyloid was regarded as portal amyloid with respect to distribution pattern. Pulmonary vascular amyloid deposits of unknown origin were observed in 12 cases (18.8%). These amyloid deposits were found mainly in medium-sized veins in the lungs and did not react with any antibodies against amyloid fibril proteins except apolipoprotein E and amyloid P component. Eleven of the 26 cases (42.3%) showing portal amyloid also showed pulmonary vascular amyloid of unknown origin. The pulmonary vascular amyloid deposits were similar to the portal amyloid deposits with respect to their morphological features and their relation to elastic fibers in the vessels. Further morphological investigation and biochemical analysis of the pulmonary vascular amyloid and portal amyloid will resolve questions of their origins and relation.     

Exogenous endothelin-1 causes peripheral insulin resistance in healthy humans

In states of insulin resistance, increased plasma levels of endothelin-1 and a disturbed vascular reactivity have been reported. In order to investigate the effects of endothelin-1 on peripheral insulin sensitivity and the vasoactive interactions between insulin and endothelin-1, six healthy subjects were studied on two different occasions with the euglycaemic hyperinsulinaemic clamp technique combined with an intravenous infusion of either endothelin-1 (4 pmol kg^?1 min^?1) or 0.9% sodium chloride. During the endothelin-1 infusion, arterial plasma endothelin-1 levels rose 10-fold. The endothelin-1 infusion reduced insulin sensitivity as demonstrated by a 31 ± 7% decrease in whole-body glucose uptake (P < 0.05) and a 26 ± 11% fall in leg glucose uptake (P < 0.05) compared with the control protocol. During the state of hyperinsulinaemia, exogenous endothelin-1 increased mean arterial blood pressure by 8 ± 1% (P < 0.05) and decreased splanchnic and renal blood flow by 30 ± 6% (P < 0.001) and 20 ± 4% (P < 0.001), respectively. However, the endothelin-1 infusion did not lower skeletal muscle blood flow measured as leg and forearm blood flow. In summary, exogenous endothelin-1 induced insulin resistance in healthy humans by reducing insulin-dependent glucose uptake in skeletal muscle without decreasing skeletal muscle blood flow. Furthermore, endothelin-1 also preserved its vasoactive potency in the presence of hyperinsulinaemia.     

Acute neurohormonal responses to hypoxaemia in man

We have studied the integrated neuroendocrine and haemodynamic effects of acute hypoxaemia in ten healthy volunteers studied on two separate occasions. After reaching a resting haemodynamic state, subjects breathed either room air or a nitrogen/oxygen mixture which rendered arterial oxygen saturation between 75% and 80%. Measurements of pulmonary and systemic haemodynamics were made and blood samples taken at baseline and after 30 min breathing air or the hypoxic gas. Blood was assayed for plasma sodium and potassium, renin-angiotensin-aldosterone system activity, natriuretic peptides, cortisol and catecholamines. Hypoxaemia significantly increased heart rate, cardiac output and mean pulmonary artery pressure (P _pa), but not mean arterial pressure compared with normoxaemia. Although plasma renin activity, angiotensin II and cortisol were unaffected by hypoxaemia, plasma aldosterone fell significantly in comparison with normoxaemia. This was associated with an increase in plasma atrial natriuretic peptide (ANP) but not b-type natriuretic peptide (BNP) during hypoxaemia whilst no changes were observed during normoxaemia. The increase in plasma ANP correlated positively with the increase inP _pa. During hypoxaemia there is therefore dissociation of the renin-angiotensin-aldosterone system where plasma aldosterone decreased, despite there being no effects on plasma renin activity and angiotensin II or on plasma cortisol. This dissociation may be due to increased levels of ANP but not BNP having specific inhibitory effects on aldosterone biosynthesis. ANP increased in proportion to the degree of pulmonary vasoconstriction induced by hypoxaemia which may indicate a counter-regulatory role.     

Effects of Histamine,Vasopressin, and Angiotensin II on Hepatosplanchnic Hemodynamics,Liver Function,and Hepatic Metabolism in Cats

Continuous i. v. infusions of histamine (5μg/kg·min), vasopressin (10 μ/kg·min), or angiotensin 11 (0.5,μg/kg·min) were given to fasting cats. Hepatic arterial flow was decreased 30% by histamine, increased 30% by vasopressin, and not significantly affected by angiotensin, whereas portal venous flow was increased 25% by histamine, decreased 40% by vasopressin, and not significantly affected by angiotensin. The hepatic arterial conductance was decreased about 25 % by histamine and angiotensin, and not significantly affected by vasopressin. The gastrointestinal conductance was decreased about 40 % by vasopressin and angiotensin, and increased 25 % by histamine. The conductance in the intrahepatic low pressure vessels was not affected by histamine and vasopressin, but decreased 25% during the infusion of angiotensin. These hemodynamic effects, however, were not accompanied by changes in the liver function or hepatic metabolism as judged from the splanchnic elimination of ethanol, the hepatic uptake and excretion of ICG, the hepatic oxygen consumption, and lactate and ketone production. This indicates that the functional capacity of the liver and thereby the number of sinusoids perfused is not markedly influenced by these drugs. Vasopressin caused a decrease in the oxygen consumption and an increase in the lactate production in the prehepatic splanchnic area, which may be due to a redistribution of the gastrointestinal blood flow.     

Angiotensin II and renal prostaglandin release in the dog. Interactions in controlling renal blood flow and glomerular filtration rate

The relationship between angiotensin II and renal prostaglandins, and their interactions in controlling renal blood flow (RBF) and glomerular filtration rate (GFR) were investigated in 18 anaesthetized dogs with acutely denervated kidneys. Intrarenal angiotensin II infusion increased renal PGE₂ release (veno-arterial concentration difference times renal plasma flow) from 1.7 ± 0.9 to 9.1 ±0.4 and 6-keto-PGFja release from 0.1 ±0.1 to 5.3 ± 2.1 pmol min^-1. An angiotensin II induced reduction in RBF of 20% did not measurably change GFR whereas a 30% reduction reduced GFR by 18 ± 8%. Blockade of prostaglandin synthesis approximately doubled the vasocon-strictory action of angiotensin II, and all reductions in RBF were accompanied by parallel reductions in GFR. When prostaglandin release was stimulated by infusion of arachidonic acid (46.8± 13.3 and 15.9± 5.4 pmol min^-1 for PGE₂, and 6-keto-PGFja, respectively), angiotensin II did not change prostaglandin release, but had similar effects on the relationship between RBF and GFR as during control. In an ureteral occlusion model with stopped glomerular filtration measurements of ureteral pressure and intrarenal venous pressure permitted calculations of afferent and efferent vascular resistances. Until RBF was reduced by 25–30% angiotensin II increased both afferent and efferent resistances almost equally, keeping the ureteral pressure constant. At greater reductions in RBF, afferent resistance increased more than the efferent leading to reductions in ureteral pressure. This pattern was not changed by blockade of prostaglandin synthesis indicating no influence of prostaglandins on the distribution of afferent and efferent vascular resistances during angiotensin II infusion. In this ureteral occlusion model glomerular effects of angiotensin II will not be detected, and it might well be that the shift from an effect predominantly on RBF to a combined effect on both RBF and GFR induced by inhibition of prostaglandin synthesis is located to the glomerulus. We therefore postulate that renal prostaglandins attenuate the effects of angiotensin II on glomerular surface area and the filtration barrier, and not on the afferent arterioles as previously suggested.     

Mechanical abdomino/heart/lung interaction

SUMMARY  It is generally assumed that inspiration will enhance both superior and inferior vena cava (SVC and IVC) blood flows due to the decrease in right atrial pressure produced by the fall in intrathoracic pressure. However, inspiration can also increase abdominal pressure due to the descent of the diaphragm. Using a model of abdominal vascular zone conditions, analogous to pulmonary vascular zone conditions, the abdominal venous compartment can be viewed as either a capacitor (zone III abdomen) or as a collapsible Starling resistor (zone II abdomen). This dual nature of the abdominal venous bed can explain how an inspiratory increase in abdominal pressure can increase IVC flow with hypervolaemia, but increase IVC flow with hypovolaemia. Combined generalized increases in abdominal pressure and focal forces over the liver can be shown to be an essential element in the pathogenesis of a Kussmaul's sign. Increases in abdominal pressures produced by active diaphragmatic descent can increase the total IVC venous return by enhancing the splanchnic IVC flow under relatively hypervolaemic conditions, but decrease the total IVC venous return by impeding the non-splanchnic IVC flow under hypo-volaemic conditions. Results are presented which suggest that the concept of abdominal vascular zone conditions is useful to understand overall directions of changes in total and regional venous return during normal and obstructed breathing and may provide useful analysis of the haemodynamic events which occur in obstructive sleep apnoea.     

Plasma angiotensins and human forearm circulation: effects of sympatho-adrenal activation

Complex interactions appear to exist between the renin–angiotensin system and sympathetic neurotransmission, and sympathetic activity may influence local angiotensin II formation. Arterial and forearm venous plasma levels of angiotensin I and II were therefore studied in 11 healthy males at rest, during sympathetic activation elicited by mental stress, and during adrenaline induced vasodilation. Specific assays for angiotensin-(1–8) octapeptide and for angiotensin-(1–10) decapeptide (i.e. angiotensin II and I, respectively), were used. Special precautions to minimize ex vivo formation and/or degradation of angiotensins were employed. Mental stress increased regional noradrenaline overflow three-fold, with a concomitant three-fold increase in forearm blood flow, whereas intravenous adrenaline infusion increased forearm blood flow two-fold and noradrenaline overflow four-fold. There was a constant positive veno-arterial concentration difference for angiotensin I under all conditions tested, compatible with local angiotensin I formation. We found no veno-arterial concentration difference for angiotensin II or regional net angiotensin II overflow under the conditions tested. These results in the forearm circulation support previous animal experimental evidence in skeletal muscle and provide no evidence in favour of a de novo formation of angiotensin II in skeletal muscle in vivo during basal conditions. Furthermore, sympathetic nerve stimulation does not seem to enhance angiotensin II generation importantly in this vascular bed.     

Effects of regulatory peptides on DNA synthesis in duodenal smooth muscle tissues of albino rats during the early postnatal period

Effects of angiotensin II, endothelin-1, dermorphin A10 analogue, dalargin, and hydra peptide morphogen on DNA synthesis in duodenal smooth muscle cells of newborn albino rats were studied by³H-thymidine autoradiography. Angiotensin II and endothelin-1 increased the number of DNA-synthesizing myocytes and did not affect the labeling intensity. Dermorphin A10 analogue, dalargin, and hydra peptide morphogen had no effect on these indexes. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 127, No. 6, pp. 651–653, June, 1999     

Plasma levels of endothelin-1 and atrial natriuretic peptide in men during a 2-hour stay in a cold room

Male volunteers were exposed to +10° C ambient temperature for 2 hours while they were sitting undressed. The levels of endothelin-1 and atrial natriuretic peptide were determined by radioimmunoassays. Control samples were obtained at thermoneutrality. The cold exposure resulted in lowering of the mean skin temperature (from 31.2± 0.3°C-22.6 ± 2.5°C, mean ± SEM), which indicates that a marked vasocon-striction took place, as well as a decrease of the body heat content (by 11.2 ± 0.7 kJ kg^-1). However, plasma endothelin-1 levels did not change significantly during the exposure. Thus circulating endothelin-1 does not seem to be responsible for the vasoconstriction associated with cold air exposure. The plasma atrial natriuretic peptide levels exhibited a slight increase towards the end of the cold exposure. This finding is in accord with the notion that atrial natriuretic peptide might contribute to the diuresis frequently observed in the cold.     

The responses of the hepatic and splanchnic vascular beds to vasopressin in rats

Vasopressin, a vasoactive peptide, causes vasoconstriction via V1a vasopressin receptors. Unlike other vasoconstrictor agents, vasopressin also has vasodilatory properties. The purpose of this study was to determine the effect of vasopressin on hepatic and splanchnic circulation in Sprague- Dawley rats. The experiments were conducted in not only isolated blood- and constant flowperfused livers but also anesthetized spontaneously breathing rats. In anesthetized rats, portal venous pressure (Ppv), systemic arterial pressure (Psa), central venous pressure, and hepatic blood flow (HBF) of combined portal venous and hepatic arterial blood flow were continuously measured, and splanchnic vascular bed resistance (Rspl) defined by (Psa - Ppv) / HBF was determined. In perfused livers, vasopressin at 0.1-1,000 nM caused weak venoconstriction as evidenced by small increase in Ppv. In anesthetized rats, when vasopressin was injected into the portal vein as a bolus consecutively at 0.01-100 nmol/kg, Psa increased dose-dependently with the peak increment of 60 ± 18 mmHg at 100 nmol/kg. Ppv and HBF decreased, with resultant increase in Rspl, indicating splanchnic vasoconstriction. In conclusion, hepatic venoconstrictor action of vasopressin was weak in rats. Vasopressin causes splanchnic vasoconstriction, resulting in a decrease in HBF and Ppv in anesthetized rats.     

Effects of hypovolaemia or isoprenaline infusion on the sympathetic reflex response to PEEP ventilation in rats

The aim of this investigation was to study vagally mediated sympathetic reflex responses to mechanical ventilation with positive end-expiratory pressure (PEEP), during hypovolaemia or during high inotropic stimulation of the heart by isoprenaline infusion. Renal sympathetic nerve activity (RSNA), heart rate and mean arterial pressure were studied during mechanical ventilation with zero end-expiratory pressure (ZEEP) and 5 and 10 cmH₂O PEEP in chloralose anaesthetized Wistar rats. Experiments were performed on two groups of rats: eight animals were subjected to 10% blood volume depletion, and seven animals to infusion of isoprenaline. PEEP ventilation was applied during control conditions and during hypovolaemia or isoprenaline infusion before and after vagotomy. In the intact (control) situation, there was a significant increase in RSNA from ZEEP to 10 PEEP in both groups (+ 75%, + 51%). During hypovolaemia or isoprenaline infusion, PEEP ventilation did not induce any significant increase in RSNA in both groups after vagotomy, 10 PEEP induced a significant increase in both groups (+ 56%, +54%). These results indicated that under conditions of hypovolaemia or increased cardiac inotropism, PEEP ventilation may elicit a vagally mediated reflex with an inhibitory action on sympathetic activity, in turn probably caused by an activation of left ventricular receptors.     

Plasma levels of endothelin-1 and atrial natriuretic peptide in men during a 2-hour stay in a cold room.

Male volunteers were exposed to +10 degrees C ambient temperature for 2 hours while they were sitting undressed. The levels of endothelin-1 and atrial natriuretic peptide were determined by radioimmunoassays. Control samples were obtained at thermoneutrality. The cold exposure resulted in lowering of the mean skin temperature (from 31.2 +/- 0.3 degrees C-22.6 +/- 2.5 degrees C, mean +/- SEM), which indicates that a marked vasoconstriction took place, as well as a decrease of the body heat content (by 11.2 +/- 0.7 kJ kg-1). However, plasma endothelin-1 levels did not change significantly during the exposure. Thus circulating endothelin-1 does not seem to be responsible for the vasoconstriction associated with cold air exposure. The plasma atrial natriuretic peptide levels exhibited a slight increase towards the end of the cold exposure. This finding is in accord with the notion that atrial natriuretic peptide might contribute to the diuresis frequently observed in the cold.     

Effect of several vasoactive agents on guanylate cyclase activity in isolated rat brain microvessels

We tested the ability of the following putative vasoactive agents to stimulate guanylate cyclase activity in isolated rat cerebral microvessels: angiotensin II, arginine vasopressin, atrial natriuretic peptide, bradykinin, carbachol and thrombin; at concentrations ranging between 10(-3) and 10(-9) M. The ability of cerebral microvessels to increase their cyclic GMP generation was ascertained in the presence of sodium nitroprusside. Of all the agents tested, only atrial natriuretic peptide stimulated cyclic GMP generation in isolated rat cerebral microvessels. Such stimulation was dose-dependent, reaching its maximum at 1 microM concentration. These results are consistent with the finding of atrial natriuretic peptide receptors in brain microvessels, and suggest that this peptide has an important role in modulating the function of brain capillaries, which constitute the blood-brain barrier. If receptors for the other vasoactive agents exist in brain microvessels, their action does not seem to be mediated by cyclic GMP as a second messenger.     

Vasoactive intestinal peptide regulates angiotensin II catabolism in the rabbit

Although vasoactive intestinal peptide (VIP) is natriuretic it stimulates renin and aldosterone secretion. Therefore, to effect a natriuresis, VIP may need to modulate the sodium conserving actions of the renin angiotensin system (RAS) by another means. One possibility is that it alters the rate of disappearance from the circulation of one or more components of the RAS. We sought to determine whether VIP regulates the rate of catabolism of angiotensin II (Ang II). Steady state metabolic clearance studies of Ang II were undertaken with and without simultaneous VIP infusion. These studies were performed in rabbits on low, normal and high sodium diets, as dietary sodium has been shown to affect the metabolism of both VIP and Ang 11. The effects of VIP on plasma Ang 11 concentration and secretion were also studied. VIP decreased Ang II catabolism in rabbits on low (P < 0.05) and normal sodium diets (P < 0.05). Plasma levels of Ang II increased significantly in response to VIP in rabbits on these diets (low, P < 0.04; normal, P < 0.05). In contrast, in rabbits on a high sodium diet VIP increased the rate of catabolism of Ang II (P < 0.001). Thus we conclude that the effect of VIP on sodium excretion may be modulated by its effects on Ang II metabolism. The decrease in Ang II catabolism seen in rabbit on low and normal sodium diets may prevent or ameliorate any natriuresis while the more rapid degradation of Ang II which occurs in dietary sodium excess may enhance the natriuretic effect of VIP.     

Importance of the renin–angiotensin system in the regulation of arterial blood pressure in conscious mice and rats

Aim: The present experiments were designed to determine the mechanism(s) for increased sensitivity to blockade of the renin–angiotensin system in mice in comparison with rats. Methods: Mice and rats, with indwelling femoral arterial and venous catheters, were chronically administered angiotensin II or pharmacological inhibitors of the renin–angiotensin system as sodium intake was altered. Results: Increasing sodium intake led to suppression of circulating renin, angiotensin II, and aldosterone in rats and mice in the absence of alterations in arterial blood pressure. Additional experiments demonstrated that continuous intravenous infusion of angiotensin II (20 ng kg^?1 min^?1) significantly increased arterial blood pressure by approximately 35 mmHg in conscious rats at all levels of sodium intake (n = 6). In contrast, arterial pressure was unaffected by angiotensin II infusion in conscious mice under conditions of low sodium intake, although arterial pressure was increased by 16 mmHg when mice were administered a high sodium intake while infused with angiotensin II (n = 6). In comparison, blockade of the endogenous renin–angiotensin system led to significantly greater effects on arterial pressure in mice than rats. Continuous infusion of captopril (30 μg kg^?1 min^?1) or losartan (100 μg kg^?1 min^?1) resulted in a 55–90% greater fall in blood pressure in conscious mice in comparison with conscious rats. Conclusion: The present studies indicate that arterial pressure in mice is more dependent upon the endogenous renin–angiotensin system than it is in rats, but mice are more resistant to the hypertensive effects of exogenous angiotensin II.