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Biomedical subjects

J F Liard

Publications and source records attributed to J F Liard.

At least 37 records · Page 2Linked to original sources
PubMed1988

Vasodilation induced by a specific vasopressin V2 agonist in dogs.

Vasopressin V2 agonists increase cardiac output and lower total peripheral resistance within minutes when infused into conscious dogs. The purpose of this study was to determine the mechanisms of these haemodynamic effects. Two groups of dogs were studied. In the first group, six dogs were instrumented for the measurement of mean arterial pressure and cardiac output (electromagnetic flowmeter) at least 1 week before the experiment. They were then anaesthetized with pentobarbital and the central nervous system was destroyed. Mean arterial pressure was maintained with an infusion of noradrenaline. After it had remained stable for 30 min the dogs received an intravenous infusion of 4-valine-8-D-arginine vasopressin (VDAVP), a specific V2 agonist, 10 ng/kg per min. Mean +/- s.e.m. arterial pressure fell from 97.6 +/- 1.8 to 69.1 +/- 2.5 mmHg, but cardiac output did not change significantly. Total peripheral resistance fell from 1322.5 +/- 151 to 859.7 +/- 84.9 units. Thus, VDAVP exerts haemodynamic effects in the absence of the central nervous system and appears to act primarily as a vasodilator. A second group of six anaesthetized dogs was studied in which femoral blood flow was measured with an electromagnetic flow probe during intravenous and intrafemoral arterial infusion of VDAVP, 10 ng/kg per min. Blood flow increased by 27.9 +/- 5.4 ml/min from a control value of 65.1 +/- 12.6 ml/min with intra-arterial infusion of VDAVP, but did not change significantly with intravenous infusion. Mean arterial pressure remained unchanged under both conditions.(ABSTRACT TRUNCATED AT 250 WORDS)

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PubMed1988

V1 vs. combined V1+V2 vasopressin blockade after hemorrhage in conscious dogs.

We examined the hypothesis that V2-like receptors might contribute to the hemodynamic response seen after blockade of the vasoconstrictor (V1) effect of arginine vasopressin (AVP) in nonhypotensive hemorrhage. Seven chronically instrumented dogs were bled 15 ml/kg within 15 min on two different days, at least 3 days apart, and then injected either with the V1 antagonist [1-(beta-mercapto-beta,beta-cyclopentamethylenepropionic acid)2-(O-methyl)tyrosine]AVP [d(CH2)5Tyr(Me)AVP, 10 micrograms/kg] or with the combined V1+V2 antagonist [1(beta-mercapto-beta,beta-cyclopentamethylenepropionic acid)2-(O-ethyl)-D-tyrosine)4-valine]AVP [d(CH2)5-D-Tyr-(Et)VAVP (10 micrograms/kg)]. Mean arterial pressure, heart rate, and cardiac output (electromagnetic flowmeter) were measured before as well as after hemorrhage and for 10 min after antagonist administration. Both antagonists given after hemorrhage significantly decreased mean arterial pressure as well as total peripheral resistance and increased cardiac output. The V1 antagonist also increased heart rate significantly. No significant hemodynamic changes were measured in another group of six dogs in the absence of antagonist treatment. Although hemodynamic changes tended to be greater with the V1 antagonist than with the combined V1+V2 antagonist, a significant difference between the two analogues was established only for heart rate. These results indicate that in hemorrhage interaction with V2-like receptors plays only a modest role in the hemodynamic changes after V1 blockade in conscious dogs, contrary to what was found in dehydration.

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PubMed1988

Vasopressin and arterial pressure regulation. Special lecture.

Data from conscious rats, dogs, and humans show that plasma arginine vasopressin (AVP) begins to exert vasoconstrictor activity at concentrations in the same range as those associated with maximum antidiuretic activity. Minimum pressor responses are observed with elevated plasma AVP, due in part to decreases of cardiac output and in part to withdrawal of sympathetic neural tone to various regions of the systemic circulation. These responses appear to some extent to be species-dependent. In conscious dogs, but not in rats, the fall of cardiac output is mediated by AVP stimulation of baroreceptor reflex pathways. Studies in rats indicate that AVP inhibits the sympathetic nervous system by direct action on the central nervous system. No evidence was found for inhibition at peripheral sites such as autonomic ganglia or vascular smooth muscle receptors. Also, AVP plays an important role in the regulation of arterial pressure with blood loss by direct vasoconstriction and by AVP enhancement of the strength of the baroreceptor reflex responses. The role of AVP in the long-term control of arterial pressure and in hypertension remains controversial, but plasma AVP is elevated in many experimental and human forms of hypertension. The link between plasma AVP and hypertension remains unclear because long-term elevation of AVP alone cannot sustain volume expansion or hypertension, and excess AVP does not enhance hypertension produced by sodium-retaining hormones or other vasoconstrictor agents. It appears that AVP plays mainly a permissive role by its fluid-retaining effects in most forms of hypertension. It is also possible that it acts as a central nervous system neural transmitter and modifies autonomic pathways in some forms of hypertension.

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PubMed1988

Characterization of acute hemodynamic effects of antidiuretic agonists in conscious dogs.

Conscious dogs instrumented for the measurement of arterial pressure and cardiac output (electromagnetic flowmeter) received intravenous injections of 4-valine-8-D-arginine vasopressin (VDAVP) and 1-deamino-8-D-arginine vasopressin (dDAVP), two specific antidiuretic agonists. Both agents led within minutes to dose-dependent increases in cardiac output and heart rate, as well as to decreases of total peripheral resistance and mean arterial pressure. Indomethacin did not affect the hemodynamic responses to VDAVP administration. The analog 8-arginine-9-desglycinamide vasopressin, which retains behavioral effects of vasopressin but is a weak antidiuretic agonist, showed only weak hemodynamic effects that were similar in nature to those of VDAVP and dDAVP. Thus, the capability to increase cardiac output and decrease peripheral resistance appeared to correlate best with the antidiuretic activity of the three vasopressin analogs tested. We also observed that pretreatment of dogs with a combined vasopressor (V1) and antidiuretic (V2) vasopressin antagonist completely prevented the increase in cardiac output that is normally associated with the infusion of arginine-vasopressin, 10 ng kg-1 min-1, after V1 blockade. Our results confirm the existence of powerful, dose-related hemodynamic effects of various antidiuretic agonists in conscious dogs; these effects being opposite to those normally elicited by arginine-vasopressin.

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PubMed1987

Effect of AVP on pressor responses to peripheral sympathetic stimulation in the rat.

Studies were carried out to determine whether arginine vasopressin (AVP) could modulate pressor responses to peripheral sympathetic stimulation or potentiate systemic norepinephrine (NE) vasoconstrictor effects. The effects of graded 30-min infusions of AVP (0.02, 0.2, and 2.0 ng X kg-1 X min-1) on the pressor responses to either electrical stimulation of spinal sympathetic outflow or NE injection (0.1, 0.5, and 1.0 micrograms/kg) were determined in central nervous system-ablated rats. Spinal stimulation with increasing frequency (0.25, 0.5, and 1.0 Hz, n = 8) at a constant voltage (20 V) or increasing voltage (8, 10, 15, and 20 V, n = 6) at a constant frequency (1 Hz) elicited significant stimulus-response relationships in mean arterial pressure (MAP). Similarly, NE increased MAP in a dose-related manner. AVP had no significant effect (P less than 0.05) on pressor responses to increasing frequency or voltage stimulation or to NE injection. We conclude that pressor responses to sympathetic stimulation in the rat are not modulated by actions of AVP to inhibit peripheral sympathetic ganglionic transmission or potentiate NE vasoconstrictor effects.

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PubMed1987

Does vasopressin-induced vasoconstriction persist during prolonged infusion in dogs?

I have examined the systemic and regional hemodynamic effects of an intravenous arginine vasopressin (AVP) infusion at a rate of 220 pg X kg-1 X min-1 maintained for 48 h in 12 conscious dogs. Plasma AVP concentration increased from 2.8 +/- 1.1 to 8.2 +/- 1.4 pg/ml, and plasma osmolality fell from 294.8 +/- 1.4 to 287.1 +/- 1.5 mosmol/kg. Mean arterial pressure increased slightly but significantly despite a reduction in blood volume. Contrary to what we previously observed with 1-h AVP infusion at the same rate, cardiac output and heart rate did not decrease, and total peripheral resistance did not increase. Most vascular beds sensitive to the acute vasoconstrictor effects of AVP, such as those of the skeletal muscle, fat, colon, and skin, did not show any significant reduction in blood flow after 48 h. Only in the pancreas and in the thyroid gland was there a significant flow decrease, which was similar in magnitude to that measured after 1 h of infusion. It therefore appears that vasoconstriction induced by modest increases in plasma concentrations of AVP is not maintained during prolonged administration in most vascular beds. However, injection of a specific antagonist of the pressor action of AVP [1-(beta-mercapto-beta,beta-cyclopentamethylenepropionic acid), 2-(O-methyl)tyrosine]arginine vasopressin, 10 micrograms/kg, induced a significant increase in cardiac output and heart rate, as well as a fall in total peripheral resistance and significant increases in myocardial, fat, and skin blood flows after 48 h of AVP infusion.(ABSTRACT TRUNCATED AT 250 WORDS)

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PubMed1986

Effects of intra-arterial arginine-vasopressin infusions on peripheral blood flows in conscious dogs.

We reported in an earlier study that intravenous infusions of arginine-vasopressin (AVP), 220 pg min-1 kg-1 for 1 h, substantially reduced blood flow to the skin, skeletal muscle, pancreas, colon, small intestine, abdominal fat and myocardium in conscious dogs. In the present study, we infused AVP directly into the artery supplying these organs and tissues in order to determine the relative contribution of local versus systemic mechanisms in the vascular resistance changes previously observed. Regional blood flows were measured with radioactive microspheres in conscious, chronically instrumented dogs before and during intra-arterial infusions of AVP administered into the left axillary artery (n = 6), the left coronary artery (n = 6), and the cranial mesenteric artery (n = 6). The infusion rates were calculated to increase local, target organ plasma concentrations of AVP to the levels reached in our previous study while minimizing systemic changes. Left axillary AVP artery infusion significantly reduced skin and compact bone blood flow, but had no effect on skeletal muscle blood flow. Intracoronary AVP infusion had no effect on myocardial blood flow nor on cardiac output. Intramesenteric AVP infusion had no effect on blood flow to the colon, small intestine and abdominal fat, but significantly reduced blood flow to those areas of the pancreas which received blood from the cannulated artery. Measurements in a limited number of dogs indicated that the local axillary and mesenteric venous levels of AVP were similar when the hormone was infused systemically at a rate of 220 pg min-1 kg-1 or intra-arterially at a lower rate.(ABSTRACT TRUNCATED AT 250 WORDS)

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PubMed1986

Regional blood flows in running normotensive and renal hypertensive dogs.

The influence of short-term hypertension on the haemodynamic response to exercise was studied by measuring arterial pressure and regional blood flow (radio-active microspheres) in dogs at two levels of treadmill exercise (5 km/h at 0 degrees and 10 km/h at 4.5 degrees). One group of dogs (n = 5) had one-kidney, one clip hypertension of 1-week duration and was compared to normotensive controls (n = 5). Both groups exhibited similar increases in heart rate, but arterial pressure increased only in the normotensive dogs. Left ventricular myocardial blood flow increased significantly in both groups. However, the increase was more pronounced in the hypertensive dogs. In some groups of active skeletal muscles (biceps brachii, tibialis cranialis), increases in blood flow in excess of 30-fold were observed during exercise in normotensive animals. Several muscles showed exaggerated increases in flow in hypertensive dogs. Perfusion of the brain, the kidneys and the splanchnic area was not compromised in either group of dogs. We conclude that in one-kidney, one clip hypertension of 1-week duration, when structural cardiovascular changes are presumably far from being completely developed, vasodilatation to increased metabolic demands in the myocardium and in most skeletal muscles is not limited in response to mild to moderate levels of exercise, and that perfusion of other vascular beds is not compromised.

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PubMed1986

Cardiovascular effects of vasopressin: some recent aspects.

We first discuss the question of direct versus indirect mechanisms in the vasoconstrictor effects induced by low plasma levels of arginine vasopressin (AVP). By infusing AVP directly into the arteries supplying various organs and tissues and measuring regional blood flows with radioactive microspheres in conscious dogs, it was determined that the increase in resistance measured after systemic administration of small amounts of AVP in the skeletal muscle, small intestine, colon, and abdominal fat results in large part from indirect mechanisms. Direct vasoconstrictor effects of AVP at these plasma concentrations were limited to the skin, the pancreas, and the compact bones. We then consider the question of cardiovascular effects of AVP from its antidiuretic activity. In the presence of a vascular antagonist, AVP decreased peripheral resistance and increased cardiac output in conscious dogs. An analog with selective antidiuretic activity, VDAVP, produced the same effects as the combination of vasopressin plus vascular antagonist. These data indicate that vasopressin, by its antidiuretic activity, produces cardiovascular effects that are opposed to many of those produced by its vasoconstrictor action. Studies in 48-h dehydrated dogs showed that part of the hemodynamic response to blockade of the vasoconstrictor action of vasopressin under these conditions is caused by unmasking cardiovascular effects linked to the antidiuretic activity of the arginine vasopressin molecule.

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PubMed1986

Cardiovascular effects associated with antidiuretic activity of vasopressin after blockade of its vasoconstrictor action in dehydrated dogs.

In view of our previous findings that a specific antidiuretic (V2) agonist, 4-valine-8-D-arginine vasopressin, acutely increased cardiac output and heart rate in dogs, we examined the hypothesis that interaction with V2-like receptors might contribute to the hemodynamic response seen after blockade of the vasoconstrictor (V1) effect of arginine-vasopressin in dehydrated dogs. After 48 hours of water restriction which increased plasma vasopressin to 10.6 +/- 2.0 pg/ml, the V1 antagonist 1-(beta-mercapto-beta,beta-cyclopentamethylene propionic acid) 2-(O-methyl)tyrosine arginine-vasopressin, 10 micrograms/kg, was injected intravenously into six conscious dogs, and the combined V1 + V2 antagonist 1-(beta-mercapto-beta,beta,cyclopentamethylene propionic acid) 2-(O-ethyl)-D-tyrosine, 4-valine arginine-vasopressin, 10 micrograms/kg, was administered to another six dogs. Mean arterial pressure, cardiac output (electromagnetic flowmeter), and regional blood flows (radioactive microspheres) were measured before and 20-30 minutes after antagonist administration. Mean arterial pressure did not change significantly in either instance. Cardiac output increased by 31.0 +/- 7.1% after V1 blockade, but by only 10.8 +/- 2.1% following V1 + V2 blockade. Blood flow increased significantly and to a similar extent in the skin, the skeletal muscles, and the fat following both antagonists. Conversely, kidney, arterial liver, and bone blood flow increased only after V1 blockade. In six additional, normally hydrated conscious dogs, it was shown that the V1 + V2 antagonist had no significant hemodynamic effects, a finding previously established for the V1 antagonist. The V1 + V2 antagonist completely prevented the hemodynamic effects associated with administration of the V2 agonist 4-valine-8-D-arginine vasopressin, 200 ng/kg, whereas the V1 antagonist did not. Both antagonists had similar effects on the hemodynamic changes induced by nitroprusside infusion, namely a potentiation of the blood pressure lowering action. These results suggest that part of the hemodynamic response to blockade of the vasoconstrictor action of vasopressin in dehydration is caused by unmasking cardiovascular effects linked to the antidiuretic activity of the arginine-vasopressin molecule.

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PubMed1986

Relationship between body fluid volumes and arterial pressure.

The mechanisms by which blood volume influences arterial pressure in situations of reduced excretory capacity are reviewed. The relationships between volume and arterial pressure are discussed as acute, transitional, and long-term phases, recognizing that they are part of a continuum of events leading to a steady state. The acute hydraulic effects, reflex and hormonal responses, and local autoregulatory responses and their interactions are reviewed. Important functional changes of the microcirculation that occur in the transitional phase (1-2 days) are presented. These include increased O2 sensitivity, elevated tone, increased vasomotion, and functional rarefaction, all of which appear to be mediated at the local tissue level. In situation of long-term chronic volume expansion, some of these functional changes evolve into permanent structural changes such as anatomical rarefaction. However, increased vascular sensitivity to oxygen remains. These changes appear to account for a maintained increase in total peripheral resistance with hypertension, which is sustained at relatively normal levels of blood volume and cardiac output.

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PubMed1985

Regional circulations in experimental coarctation of the aorta in conscious dogs.

Regional blood flows were measured with radioactive microspheres in 35 conscious dogs at various times (between 1 h and 28 days) after creation of a stenosis of the descending thoracic aorta. Mean arterial pressure increased moderately proximal to the stenosis. Distally, arterial pressure decreased below control values immediately after stenosis, then returned gradually toward preconstriction values over 28 days. Plasma renin activity increased sixfold, after aortic constriction of 1 and 6 h, and remained significantly elevated for four days. Blood volume did not change significantly. In some of the vascular beds exposed to the elevated proximal pressure, significant increases in blood flow were noted in the early stages, mainly in the myocardium, the brain, the skeletal muscles and the bones. After 28 days, however, blood flows were significantly reduced in most tissues exposed to the proximal pressure. At this stage, vascular conductance was significantly decreased in the myocardium, the brain, the muscles, the skin and the bones as compared with a sham-operated control group. Several vascular beds perfused by the distal arterial pressure also showed a significant fall in flow after 28 days, notably the small intestine, the skin, the skeletal muscles and the bones. At that stage, vascular conductance was decreased in the small intestine, the muscles, the skin and the bones. Thus, aortic coarctation in dogs was characterized by a late generalized increase in vascular resistance extending to tissues which were never exposed to increased arterial pressure nor to an increased blood flow. These findings suggest that a systemic vasoconstrictor influence overrides local mechanisms in the control of regional circulations in coarctation hypertension.

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PubMed1985

Hemodynamic effects of neurohypophyseal peptides with antidiuretic activity in dogs.

Arginine vasopressin (AVP) is known to produce increases in total peripheral resistance (TPR) and mean arterial pressure (MAP) and decreases in heart rate (HR), cardiac output (CO), and plasma renin activity (PRA). Some recent observations with AVP and synthetic analogues have suggested that under certain conditions, AVP can induce cardiovascular and reninsecretory responses in the opposite directions. To characterize the receptors mediating these responses, the effects of AVP, oxytocin, and synthetic neurohypophyseal analogues with specific antidiuretic, vasoconstrictor, or oxytocic activities were studied in conscious dogs. AVP and 2-phenylalanine-8-ornithine-oxytocin (Phe2Orn8OT, a selective vasoconstrictor agonist) produced similar responses when infused at 10 ng X kg-1 X min-1. That is, TPR and MAP increased, and CO, HR, and PRA decreased. Pretreatment with a selective vasoconstrictor antagonist, [1-(beta-mercapto-beta,beta-cyclopentamethylenepropionic acid) 2-(O-methyl)tyrosine]AVP, abbreviated d(CH2)5Tyr(Me)-AVP (10 micrograms/kg), blocked the actions of Phe2Orn8OT. However, in the presence of d(CH2)5Tyr(Me)AVP, AVP actually decreased TPR and increased CO, HR, and PRA. An analogue with selective antidiuretic activity, 4-valine-8-D-AVP (VDAVP, 10 ng X kg-1 X min-1), produced the same effects as the combination of vasopressin plus d(CH2)5Tyr(Me)AVP. Neither the effects of VDAVP nor of AVP plus antagonist were blocked by propranolol (1 mg/kg). These data indicate that vasopressin, by its antidiuretic activity, produces cardiovascular effects that are opposite to many of those produced by its vasoconstrictor action and that these effects are not dependent on mediation by beta-adrenoceptors.

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PubMed1984

Vasopressin in cardiovascular control: role of circulating vasopressin.

Vasopressin has been shown to elicit vasoconstriction in unanaesthetized animals at plasma concentrations similar to those associated with its renal antidiuretic effect. The vasconstrictor effects of vasopressin do not normally translate into pressor responses until relatively high plasma concentrations are reached. This appears to be related to very effective buffering by the baroreceptor reflex. In the absence of afferent signals from the baroreceptors (surgical denervation, but more importantly, low arterial pressure), the vasoconstriction elicited by vasopressin represents a significant part of the mechanisms that determine blood pressure. Vasopressin is clearly involved in the short-term control of blood pressure in situations such as haemorrhage, other volume-depleted states and dehydration. However, it is only one of several short-acting mechanisms which complement each other in the defence against hypotensive stresses. Under different conditions, the cardiovascular effects of vasopressin seem to have a component related to the central nervous system control of the circulation. Whether or not circulating vasopressin interacts with the newly described network of extrahypothalamic projections from the paraventricular nucleus is yet conjectural. However, the presence in the brain of vasopressin-containing pathways and of various types of receptors to vasopressin, as well as the existence of cardiovascular effects elicited by central administration of antidiuretic hormone, suggests a role for cerebral vasopressin in the control of autonomic function. Slightly elevated levels of vasopressin have been found in various forms of hypertension. Yet, the role of vasopressin, when present, may be more related to its antidiuretic than to its vasoconstrictor properties.(ABSTRACT TRUNCATED AT 250 WORDS)

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PubMed1984

Plasma vasopressin levels after infusions of hypertonic saline solutions into the renal, portal, carotid, or systemic circulation in conscious dogs.

To determine whether extracerebral osmoreceptors contribute to vasopressin release when exposed to blood osmolality changes of about 1%, we administered hypertonic saline solution to five conscious dogs through catheters chronically implanted into the inferior vena cava, the portal vein, the artery to a sole remaining kidney, and the common carotid arteries. Each infusion was given on a different day at a rate of 0.2 ml/min, which provided about 25 mumol NaCl/kg BW X min. The changes in plasma sodium concentration and plasma osmolality measured during these infusions were similar with all four routes of administration and significantly different from those after iv infusion of isotonic saline solution. Plasma vasopressin concentration, measured by RIA, increased more rapidly after intracarotid infusions than with any other route. We found no evidence that renal or portal/hepatic osmoreceptors contributed to vasopressin release under the conditions of our study.

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PubMed1984

Changes in regional vascular resistance in canine aortic coarctation.

Aortic coarctation was created experimentally in dogs and regional blood flows were measured at various times thereafter with radioactive microspheres in the conscious state. Mean arterial pressure increased moderately proximal to the stenosis, whereas distally it was reduced below control immediately, returning progressively toward control over 28 days. Blood flows were compared in tissues that are found both proximally and distally (skeletal muscles, skin and bones). In several groups of muscles located in the anterior part of the body, vascular conductance increased during the first hours after coarctation, then decreased below control. A similar pattern was observed in muscles of the hind leg. In the skin and in the bones of the front leg and of the hind leg, vascular conductance also increased in the early stages and decreased during the late stages. It therefore appears that aortic coarctation in dogs is characterized by a late generalized decrease in vascular conductance that extends to tissues which are never exposed to increased arterial pressure. These findings suggest that a systemic vasoconstrictor influence (possibly the measured increase in plasma renin activity) overrides local mechanisms in the control of regional circulations.

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