Electrogenic and electroneutral components of the sympathetic effect on fluid absorption in the rat jejunum

The aim of the study was to test the hypothesis that the sympathetic nerves to the jejunum enhance net fluid absorption rate by inhibiting an electrogenic flux of anions into the lumen. The design of the experiments was based on the observation that the effect of catecholamines on electrogenic transport is abolished by yohimbine, an alpha 2 adrenergic antagonist. Net electrogenic transport in jejunal segments of anaesthetized rats was estimated by measurement of the transepithelial potential difference (PD) and short-circuit current (SCC). Net fluid absorption rate was quantified by a gravimetric technique. The sympathetic nerves to the segment were stimulated electrically, both in vitro and in vivo. The effect of sympathetic nerve stimulation on SCC and net fluid transport was determined in the absence and presence of the alpha-adrenergic antagonists phentolamine (a non-selective alpha-adrenergic antagonist), prazosin (a selective alpha 1-antagonist) and yohimbine (a selective alpha 2-antagonist). Sympathetic nerve stimulation decreased PD and SCC and increased net fluid absorption rate. Phentolamine abolished both the electrogenic response and the effect on net fluid absorption rate, without having any significant intrinsic effects on either parameter. Prazosin per se markedly increased net fluid absorption rate, but did not significantly influence the sympathetic effect on SCC or net fluid absorption rate. Yohimbine abolished the electrogenic effect of sympathetic stimulation, and per se increased net fluid absorption rate in innervated but not in denervated segments. In innervated segments, the absorption rate during sympathetic nerve stimulation was similar in controls and yohimbine-treated animals. In denervated segments, yohimbine significantly attenuated the sympathetic response. The results suggest that the sympathetic nerves enhance fluid absorption rate via effects on both electrogenic and electroneutral epithelial transport. These two components of the sympathetic response seem to be mediated by different alpha-receptor mechanisms.     

Effects of alpha2-adrenoceptor blockade and thyrotropin-releasing hormone (TRH) on the cardiovascular system in the rabbit

The effects of two different doses of thyrotropin-releasing hormone on regional blood flows were studied in urethane-anaesthetized rabbits pretreated with the α₂ adrenergic antagonists yohimbine and idazoxan. The effects of yohimbine were also studied using unanaesthetized rabbits. Blood flow measurements were performed using the tracer microsphere method. Thyrotropin-releasing hormone was injected i. v. at a dose of either 0.1 mg kg^-1 or 2.0 mg kg^-1. Yohimbine and idazoxan did not modify the effect of thyrotropin-releasing hormone on mean arterial blood pressure. In the anaesthetized animals, blockade of the α₂ adrenoceptors resulted in a vasoconstriction in several peripheral organs and the vasoconstriction increased after thyrotropin-releasing hormone administration. Pretreatment with yohimbine reduced total cerebral blood flow moderately and in such animals thyrotropin-releasing hormone elicited only minor cerebral blood flow effects. Pretreatment with idazoxan did not reduce the total cerebral blood flow and in such animals it increased from 53± 1 to 75±4 g min^-1 100 g^-1 (P < 0.01) after the administration of the lower dose of thyrotropin-releasing hormone and from 64±5 to 112±17 g min^-1 100 g^-1 (P < 0.01) after the higher dose. In the conscious animals, yohimbine caused an increase in mean arterial blood pressure and heart rate. Vascular resistance increased in several organs. The cerebral blood flow decreased in white matter (P <0.05) and the caudate nucleus (P < 0.05). The results indicate that there is a yohimbine-sensitive mechanism involved in the cerebrovasodilating effect of thyrotropin-releasing hormone in anaesthetized rabbits. There is also an activation of the sympathetic nervous system by thyrotropin-releasing hormone which results in increased vascular resistance and mean arterial blood pressure. Its effect on the vascular resistance may be enhanced by α₂ adrenoceptor blockade. In conscious animals, there seems to be a yohimbine-sensitive mechanism involved in the control of cerebral blood flow.     

The relative roles of the aortic and carotid sinus nerves in the rabbit in the control of respiration and circulation during arterial hypoxia and hypercapnia

1. The respiratory and circulatory effects of graded arterial hypoxia, alone or with superadded hypercapnia, were studied in four groups of unanaesthetized rabbits including normal animals and those with selective section of the aortic nerves, selective section of the carotid sinus nerves and section of both sets of nerves.

2. When measured 2-4 days after selective section of the carotid sinus nerves the resting respiratory minute volume and arterial P_O2 were lower and the P_CO2 higher than normal. These effects were not observed after selective section of the aortic nerves. Selective aortic nerve section, and selective carotid sinus nerve section each produced a similar increase in the resting arterial pressure and heart rate, but were without effect on the resting cardiac output.

3. During arterial hypoxia reflex respiratory and circulatory effects ascribable to arterial chemoreceptor stimulation (hyperventilation, bradycardia, vasoconstriction) were mediated for the most part through the carotid sinus nerve. In animals with only the aortic nerves intact the circulatory response was determined largely by the opposing effects of aortic baroreceptor reflexes and the local peripheral dilator action of hypoxia.

4. The circulatory effects of hyperventilation induced by hypercapnia during arterial hypoxia, in animals with both aortic and carotid sinus nerves cut were small.

5. The results suggest that relatively few chemoreceptor fibres originate from the aortic region in the rabbit, though the carotid sinus and aortic nerves both contain baroreceptor fibres.

     

Cardiovascular responses to changes in carotid sinus transmural pressure in man.

To study the relative importance of cardiac and peripheral effector mechanisms in the carotid sinus baro-reflex in man cardiovascular responses to equal changes of the carotid sinus transmural pressure (Ptm) in either direction of the normal were recorded and compared in eight physically well-trained young male volunteers. In both the supine and the 70 degrees head-up position, a decrease in Ptm produced a more potent reflex response of the systemic arterial pressure than did a similar increase in Ptm. Whereas the arterial pressure response to increased Ptm was due solely to a reduction in vascular resistance, a significant increase in cardiac output contributed to the more potent pressor response to a decrease in Ptm and thus to the predominantly antihypotensive properties that characterize the carotid sinus baroreceptor control system in man. However, since combined beta-adrenergic and parasympathetic blockade abolished the effect of reduced Ptm on cardiac output without greatly impairing the blood pressure response, it is concluded that adjustments in cardiac output are not of critical importance in the buffering function of the carotid sinus baroreceptors. Autonomic cardiac blockade exaggerated the fall in cardiac output on head-up tilt, the arterial pressure remaining unaffected due to a compensatory increase in systemic vascular resistance.     

Cardiovascular Responses to Changes in Carotid Sinus Transmural Pressure in Man

To study the relative importance of cardiac and peripheral effector mechanisms in the carotid sinus baroreflex in man cardiovascular responses to equal changes of the carotid sinus transmural pressure (Ptm) in either direction of the normal were recorded and compared in eight physically well-trained young male volunteers. In both the supine and the 70d? head-up position, a decrease in Ptm produced a more potent reflex response of the systemic arterial pressure than did a similar increase in Ptm. Whereas the arterial pressure response to increased Ptm was due solely to a reduction in vascular resistance, a significant increase in cardiac output contributed to the more potent pressor response to a decrease in Ptm and thus to the predominantly antihypotensive properties that characterize the carotid sinus baroreceptor control system in man. However, since combined beta-adrenergic and parasympathetic blockade abolished the effect of reduced Ptm on cardiac output without greatly impairing the blood pressure response, it is concluded that adjustments in cardiac output are not of critical importance in the buffering function of the carotid sinus baroreceptors. Autonomic cardiac blockade exaggerated the fall in cardiac output on head-up tilt, the arterial pressure remaining unaffected due to a compensatory increase in systemic vascular resistance.     

Effects of atrial natriuretic peptide (ANP) on jejunal net fluid absorption in the rat

The role of atrial natriuretic peptide (ANP) on jejunal net fluid transport was studied in intact rats as well as in rats subjected to a perivascular denervation of the intestinal segment. In rats with intact nerves, an acute volume expansion with 5% albumin (10% of estimated blood volume) decreased jejunal net fluid absorption by approximately 70% compared to control animals not subjected to volume expansion. After a perivascular denervation of the intestinal segment, the acute volume expansion reversed net fluid absorption into a net fluid secretion. In order to reduce the volume expansion-induced endogenous release of ANP, one group of rats was subjected to a right atrial appendectomy 7 days prior to the experiments. In these animals, the intestinal response to the same 10% volume load was blunted compared to controls. Administration of rat alpha-ANP (99-126; 5 micrograms kg-1 i.v.) induced effects similar to those of volume expansion both in rats with intact perivascular nerves as well as in denervated animals. Volume expansion increased mean arterial pressure (MAP) as well as central venous pressure and decreased heart rate (HR) in all groups. When exogenous ANP was administered, a fall in MAP was seen, while HR remained unchanged. In conclusion, these data strongly indicate a physiological role for ANP in jejunal fluid transfer in response to acute volume expansion.     

The effect of carotid occlusion on the rate of net fluid absorption in the small intestine of rats and cats

The effect on net intestinal fluid absorption of unloading the baroreceptors by bilateral carotid occlusion was studied in rats and cats. It was shown that net fluid uptake from the intestine increased 30–40% upon carotid occlusion. This effect was eliminated by cutting the splanchnic nerves (cats) or by severing the nerves surrounding the superior mesenteric artery (rats). In fact, these denervation procedures resulted in a decreased net fluid absorption upon carotid occlusion. Cutting the vagal nerves did not significantly influence the response to carotid occlusion. It is concluded that the arterial baroreceptors influence net fluid transport in the small intestine, a reflex compensatory mechanism that may be important in different hypotensive situations.     

The cause of the difference between the arterial baroreceptor reflex under natural pulsatile circulation and under nonpulsatile systemic circulation

In a previous study we investigated the relation between afferent and efferent activity of the arterial baroreceptor reflex under nonpulsatile systemic circulation using total left heart bypass. The results indicated that the regulation of the arterial baroreceptor reflex was converted under nonpulsatile systemic circulation, and we inferred that a possible reason for this conversion was the transformation in discharge of the afferent activity of the arterial baroreceptor reflex that took place under nonpulsatile systemic circulation. In the present study we tested this hypothesis by sectioning carotid sinus and aortic depressor nerves and electrically stimulating bilateral aortic depressor nerves under anesthesia in five rabbits (400 spikes for 20s, with 0.02ms pulse width and 8 V amplitude), while recording changes in aortic pressure, mean aortic pressure, and heart rate. Continuous stimulation was taken as discharge of the afferent activity of the arterial baroreceptor reflex under nonpulsatile systemic circulation, and periodic stimulation was taken as discharge under natural pulsatile circulation. Aortic pressure, mean aortic pressure, and heart rate decreased under both continous and periodic stimulation. The decreases in mean aortic pressure and heart rate during continuous stimulation were significantly lower than those during periodic stimulation. Our results suggest that the transformation in discharge of the afferent activity of the arterial baroreceptor reflex under nonpulsatile systemic circulation may have played an important causative role in the conversion of the regulation of the arterial baroreceptor reflex under nonpulsatile systemic circulation.     

Reflex Plasma Hyperglycemia and Hyperosmolality Evoked by Unloading of the Carotid Baroreceptors

Hemorrhage is usually accompanied by a considerable increase in the plasma osmolality and glucose concentration due to an augmented release of glucose from the liver. In the present cat experiments an attempt was made to investigate the possible role of different vascular receptors in mediating this hyperglycemic (hyperosmolar) response. Bilateral vagotomy or stimulation of the carotid chemoreceptors by perfusion of the carotid sinus with venous blood at normal pressure only slightly increased the arterial plasma glucose concentration. On the other hand, when the sinus nerves were cut in the vagotomized animal, thereby simulating complete unloading of the carotid baroreceptors, the arterial plasma glucose concentration rose by about 8 mM/L and the arterial plasma osmolality by about 10 mOsm/kg H₂O. Perfusion of the carotid baroreceptors with arterial blood at different levels of hypotension showed that the baroreceptor-induced hyperglycemia was graded in relation to the pressure level. Regional hypotension of the liver, pancreas, intestine, kidneys or brain did not significantly affect plasma glucose concentration or osmolality. We conclude that the reflex release of glucose from the liver during hemorrhage mainly is initiated from the unloading of arterial baroreceptors.     

Reflex adrenergic control of endocrine pancreas evoked by unloading of carotid baroreceptors in cats

The effects of unloading of the carotid baroreceptors on arterial plasma glucose concentration as well as on portal plasma immunoreactive glucagon (IRG) and insulin (IRI) concentrations were studied in an-estethized, vagotomized cats either by sectioning the sinus nerves or by lowering the pressure in the isolated carotid sinuses. Complete elimination of the carotid baroreceptor discharge by cutting the sinus nerves caused an increase in the arterial plasma glucose concentration by 100% and an increase in the portal IRG level by about 200%, whereas the portal IRI concentration decreased to 50% of its basal value. These baroreceptor-induced changes of the plasma IRG and IRI levels seemed to be graded in relation to the drop in carotid blood pressure and they were clearly detectable when the pressure was lowered from 120 to 90 mmHg in the isolated carotid sinus preparation. The described reflex hyperglycemia, hyperglucago-nemia and hypoinsulinemia were mediated to the pancreas and liver mainly by the sympatho-adrenal system, since cutting the splanchnic nerves above the adrenal glands abolished the hyperglycemic and hypoinsulinemic responses and markedly depressed the magnitude of the hyperglucagonemic response. In adrenalectomized cats, complete unloading of the baroreceptors evoked both hyperglucagonemia and hypoinsulinemia although the magnitude of the hormonal responses was diminished. In animals where the pancreas and liver were sympathectomized but the adrenal glands left intact, cutting the sinus nerves evoked a doubling of the IRG level and a slight increase in plasma glucose, but no significant change of the IRI level. I.v. infusion of adrenaline (1 γg/kg × min) or noradrenaline (5 γg/kg × min) caused pronounced increases in IRG and plasma glucose and a clear-cut reduction of IRI. We conclude that the function of the endocrine pancreas in the cat can be influenced by variations in the blood pressure by means of a reflex control which originates from arterial baroreceptors. This reflex adjustment of the endocrine pancreas is mediated chiefly by two links of the sympatho-adrenal system, namely by catecholamine-release from the adrenal medulla and, more importantly. by a direct adrenergic nerve fibre influence on the α- and β-cells.     

Time Course and Extent of Carotid Sinus Baroreceptor Threshold Resetting in Rats with Renovascular Hypertension

To study the extent and time course of arterial baroreceptor threshold resetting to increases in blood pressure, renal hypertension was induced in young normotensive male Wistar rats by unilateral renal artery constriction. At different intervals after operation the extent of baroreceptor threshold resetting in the carotid sinus was examined. Experiments were performed 7, 14 and 25 days after renal artery clipping to enable baroreceptor resetting to be correlated with the rate and extent of cardiovascular changes in rats which had renovascular hypertension of identical durations (Lundgren et al. 1974). Baroreceptor thresholds in the carotid sinuses were established by progressive clamping of both carotid arteries after partial vascular isolation of the sinuses. The results show that after one week of hypertension baroreceptor resetting is only just apparent but by two weeks resetting is gross and seems to be largely completed. This parallels the adaptive changes in the hindquarters of renal hypertensive rats and it is concluded that baroreceptor resetting is a secondary phenomenon related to the structural changes induced in the vessels by the elevated blood pressure.     

The effects of haemorrhage in the unanaesthetized rabbit

1. The circulatory response following acute loss of 26% of the blood volume was examined in unanaesthetized rabbits. The groups of animals studied were normal rabbits; adrenalectomized rabbits; animals subjected to prolonged treatment with guanethidine in which peripheral adrenergic nerve transmission is blocked, but which can reflexly liberate adrenal medullary hormones; animals subjected to combined adrenalectomy and guanethidine treatment with no functional adrenergic effectors; in each case with or without administration of atropine. The responses of animals with section of the carotid sinus and aortic nerves were also examined.

2. The spontaneous rate of replacement of the blood volume after haemorrhage by reabsorption of extravascular fluid was the same in all the above preparations, the blood volume returning to normal 3-4 hr after bleeding.

3. The `passive' effects of haemorrhage were examined in animals without functioning autonomic effectors and include a large fall in right atrial pressure and cardiac output, arterial hypotension, no significant change in total peripheral resistance, and a bradycardia of gradual onset. Reflex autonomic effector activity in normal animals minimizes the fall in atrial pressure, cardiac output and arterial blood pressure, and produces a significant increase in total peripheral resistance and tachycardia. Increased sympathetic nerve activity and secretion of adrenal medullary hormones each play an important and complementary part in the normal circulatory response to haemorrhage of the rabbit. There is also reflex reduction in vagal efferent activity.

4. Reflexes from the carotid sinus and aortic arch limit the fall in arterial pressure for the first 4 hr after haemorrhage. These reflexes also account for the tachycardia normally observed after haemorrhage. The baroreceptor reflexes rather than the chemoreceptors appear to be dominant in these responses.

5. Twenty-four hours after haemorrhage the haemodynamic pattern is similar in all preparations irrespective of their autonomic effector status: blood volume, right atrial pressures and cardiac outputs are all elevated, and the arterial pressure has virtually recovered, consistent with the development of hypervolaemic anaemia at this time.

     

Left ventricular inotropic and peripheral vasomotor responses from independent changes in pressure in the carotid sinuses and cerebral arteries in anaesthetized dogs

1. The pressure perfusing the isolated carotid sinuses and the pressure perfusing the cerebral circulation were changed independently, and the resulting inotropic responses in the left ventricle and peripheral vasomotor responses were determined.2. Inotropic responses were assessed by measuring changes in the maximum rate of change of left ventricular pressure (dP/dt max) with heart rate and mean aortic pressure held constant. Vascular resistance changes were usually assessed by perfusing the descending thoracic aorta at constant flow and measuring changes in perfusion pressure.3. Decreases in carotid sinus pressure over the baroreceptor sensitivity range resulted in a 45% increase in dP/dt max and a 59% increase in vascular resistance.4. Unless arterial oxygen tension was abnormally low, lowering cerebral perfusion pressure to 50 mm Hg resulted in little or no inotropic and vasomotor responses. In the presence of hypoxaemia (P(a,O2) < 60 mm Hg), lowering cerebral perfusion pressure to below about 80 mm Hg resulted in marked responses.5. These experiments suggest that, unless arterial oxygen tension is abnormally low, the carotid sinus reflex and not cerebral hypotension is important in the control of the inotropic state of the heart and of vasomotor activity. With hypoxaemia, responses from cerebral hypotension may also be important.     

Influence of carotid baroreceptors on different components of the vascular system

1. Reflex changes in wall tension of the lateral saphenous vein of one hind limb, the splenic veins and capsule, and the resistance vessels of the other hind limb caused by changes in baroreceptor activity were measured in vagotomized dogs under thiopentone-chloralose anaesthesia.2. Three different methods were used to alter pressure in one or both carotid sinuses. (1) Both carotid sinuses were vascularly isolated and filled with fully oxygenated Krebs-Ringer bicarbonate solution (pH 7.4) from a reservoir in which the pressure could be altered at will. (2) One sinus was denervated, and the contralateral sinus was perfused with arterial blood at different flow rates. (3) One sinus was denervated, and the innervated sinus was perfused with arterial blood at constant flow, the pressure being altered by changing the outflow resistance.3. The left saphenous vein was perfused at constant flow with autologous blood; changes in perfusion pressure were used as a measure of changes in veno-motor activity. The right common iliac artery was perfused at constant flow to measure changes in resistance vessel activity. Blood flow through the spleen was temporarily arrested, trapping a fixed volume of blood in the organ. Under these conditions, changes in splenic vein pressure were a measure of changes in smooth-muscle tension in the splenic capsule and veins.4. In order to assess the responses to baroreceptor stimulation in terms of alterations in sympathetic nerve traffic to different components of the peripheral vascular system, ;frequency-response curves' were constructed for spleen, saphenous vein, and limb resistance vessels by electrical stimulation of the splenic nerves and lumbar sympathetic chains.5. The saphenous vein showed no consistent response to changes in baroreceptor activity. Reduction in carotid sinus pressure from 180 to 100 mm Hg caused an increase in venous pressure in the isovolumetric spleen and in the iliac artery perfusion pressure. These results were confirmed by electrical stimulation of the carotid sinus nerve. Whereas the peak responses of the limb resistance vessels corresponded to an increase in lumbar sympathetic nerve traffic of 6-10 c/s, the maximal splenic responses were equivalent to an increase in splenic nerve traffic of 1-4 c/s. These results are consistent with selective autonomic nervous control of different components of the peripheral vascular system.     

The carotid sinus baroreceptor reflex in the pregnant rabbit

1. The reflex responses to baroreceptor stimulation have been compared in eight pregnant and eight non-pregnant anaesthetized female rabbits.2. The vascularly isolated, innervated carotid sinus was exposed for 30 sec to a series of non-pulsatile pressures ranging from 30 to 230 mmHg. The contralateral sinus nerve and both aortic nerves were cut. Systemic arterial pressure and heart rate were measured at each sinus pressure.3. The range of arterial pressure change which could be evoked from the isolated innervated sinus was less in the pregnant than in the non-pregnant rabbits. Mean changes were 98 and 61 mmHg respectively. On the other hand changes in heart rate were similar in the two groups (45 and 43 beats/min respectively).4. The smaller blood pressure response in the pregnant animals resulted from a lesser rise in systemic arterial pressure at low levels of sinus pressure. At high sinus pressures the blood pressure fell to a similar level in both groups of animals.5. Pressure on the great vessels by the gravid uterus was not a factor since there was no consistent difference between the responses obtained with the rabbit lying on its back or on its side.6. Mechanisms which might be responsible for the difference found are discussed.     

The effects of changes in the carotid sinus baroreceptor activity on splanchnic blood flow in anesthetized man

In 9 patients being subjected to abdominal surgery, electromagnetic blood flow measurements were obtained from the hepatic, mesenteric and iliac beds while the carotid sinus baroreceptors were stimulated by carotid sinus massage. Carotid sinus stimulation produced an average maximum decrease in mean arterial pressure of 21%. Hepatic and mesenteric blood flows decreased by 15% and calculated vascular resistances were not significantly changed in these vascular beds. Iliac blood flow, on the other hand, showed a slight increase and iliac vascular resistance was decreased by 29%. It is concluded that the splanchnic vascular bed is of less importance in the carotid sinus baroreflex control of systemic arterial pressure in anesthetized man.     

Depressed responsiveness of the carotid sinus reflex in conscious newborn animals.

The responsiveness of the carotid sinus reflex was evaluated by comparing the effects of bilateral carotid occlusion (BCO) in conscious adult dogs and puppies on measurements of arterial pressure, cardiac output, heart rate, and calculations of total peripheral resistance (TPR). In eight adult dogs, BCO increased mean arterial pressure by 57 +/- 6%, TPR by 48 +/- 5%, and heart rate by 45 +/- 15%. In puppies, BCO induced smaller increases (P less than 0.05) in mean arterial pressure (30 +/- 5%) and TPR (29 +/- 4%), while heart rate did not change. After elimination of opposing vagal and aortic baroreceptor reflexes, the differences in responses to BCO of mean arterial pressure and TPR between adults and newborns were even greater. Thus, the carotid baroreceptor reflex appears to be depressed in the newborn when compared with the fully developed reflex in the normal, conscious adult.     

Comparison of the reflex vasomotor responses to separate and combined stimulation of the carotid sinus and aortic arch baroreceptors by pulsatile and non-pulsatile pressures in the dog

1. In the anaesthetized dog the carotid sinuses and aortic arch were isolated from the circulation and separately perfused with blood by a method which enabled the mean pressure, pulse pressure and pulse frequency to be varied independently in each vasosensory area. The systemic circulation was perfused at constant blood flow by means of a pump and the systemic venous blood was oxygenated by an extracorporeal isolated pump-perfused donor lung preparation.2. When the vasosensory areas were perfused at non-pulsatile pressures within the normal physiological range of mean pressures, the reflex reduction in systemic vascular resistance produced by a given rise in mean carotid sinus pressure was significantly greater than that resulting from the same rise of aortic arch pressure.3. On the other hand, when the vasosensory areas were perfused at normal pulsatile pressures and within the normal physiological range of mean pressures, there was no difference in the size of the reflex vascular responses elicited by the same rise in mean pressure in the carotid sinuses and in the aortic arch.4. Whereas the vasomotor responses elicited reflexly by changes in mean carotid sinus pressure are modified by alterations in pulse pressure, those evoked by the aortic arch baroreceptors through changes of mean pressure are only weakly affected by modifications in pulse pressure. Evidence for this was obtained from single stepwise changes of mean pressure in each vasosensory area during pulsatile and non-pulsatile perfusion, and from curves relating the mean pressure in the carotid sinuses or aortic arch and systemic arterial perfusion pressure.5. The vasomotor response elicited by combined stimulation of the carotid sinus and aortic arch baroreceptors was greater than either response resulting from their separate stimulation.6. When the mean perfusion pressures in the two vasosensory areas are changed together, the curve relating mean pressure to systemic arterial pressure during pulsatile perfusion of the areas is considerably flatter than that for non-pulsatile perfusion.7. Increasing the pulse pressure in the carotid sinuses or aortic arch caused a decrease in systemic vascular resistance, the response elicited from the carotid sinuses being the larger.8. Altering the phase angle between the pulse pressure waves in the carotid sinuses and aortic arch had no effect on systemic vascular resistance.9. In both vasosensory areas, increasing the pulse frequency caused a reduction in systemic vascular resistance.     

Response of rat jejunum to angiotensin III: pharmacology and mechanism of action

At low doses angiotensin III (A III) stimulates jejunal fluid absorption in the pentobarbital sodium-anesthetized rat. In contrast, at high doses the hormone inhibits absorption and/or stimulates secretory processes. The stimulation of jejunal absorption in response to A III can be blocked by guanethidine, phentolamine, and prazosin but not by propranolol or yohimbine, suggesting that A III-increased intestinal absorption is secondary to the release of norepinephrine from sympathetic nerves in the jejunum and activation of postsynaptic alpha 1-adrenergic receptors. The A III inhibition of water absorption is not affected by adrenergic antagonists but can be reversed to a net stimulation of transfer after pretreatment of the animals with indomethacin. This suggests that at high doses A III stimulates intestinal prostaglandin biosynthesis. The A III analogue [Ile7]A III is devoid of agonist activity over a wide dose range and behaves as a potent antagonist of both the stimulatory and the inhibitory effects of the parent peptide on jejunal absorption. [Ile7]A III will be a useful tool for investigating the physiological role of angiotensin peptides in the control of intestinal absorption.     

Carviobascular alterations associated with bursts of panting in the exercising dog

1. In conscious dogs exercising on a treadmill variations in arterial blood pressure and heart rate which were correlated with bursts of panting were observed. The blood pressure variations reflected similar variations in the total peripheral vascular resistance.2. During exercise a change in respiration from slow breathing to panting was followed by a systemic vasodilatation and fall in blood pressure, but a rise in heart rate. Analysis of the time course of these effects demonstrated that the heart rate increase occurred later than the blood pressure fall.3. The correlation between panting and blood pressure changes was not abolished by either of the receptor-blocking drugs atropine sulphate or propranolol, nor by either of the following surgical procedures: acute bilateral cervical vagotomy, and denervation of the carotid sinus baroreceptors and carotid body chemoreceptors.4. The vasodilatation which followed a burst of panting appeared to be due to a decrease in adrenergic vasoconstrictor sympathetic nerve activity, and not to a change in the chemical composition of the arterial blood.5. It is concluded that the vascular changes are not reflex responses to stimulation of peripheral receptors by the bursts of panting. Instead, it is suggested that both the bursts of panting and associated falls in blood pressure are parallel effects resulting from activation at a suprabulbar level of the central nervous system. It is also concluded that the variations in heart rate are mediated by the baroreceptor reflex mechanism, activated by the changes in mean blood pressure.