Fall In Vascular Resistance Research Articles

Local control of blood flow in the dog's stomach: Vasodilatation caused by acid back-diffusion following topical application of salicylic acid

Abstract A completely isolated segment of the greater curvature of a dog's stomach, held in a plastic chamber, was perfused at a constant flow through a single artery with blood from a donor dog. Perfusion pressure was measured continuously, and vascular resistance was calculated by dividing perfusion pressure by flow. The mucosal surface was bathed with fluids held at constant temperature. No change in vascular resistance followed substitution of 160 mN HCl for 154 mN NaCl as the bathing fluid, and there was no change when atropine SO 4 (0.2 mg kg −1 ) was given to the donor. Substitution of 20 or 30 mM salicylic acid in 100 or 160 mN HCl was followed within a minute, and often within 12 sec, by a fall in vascular resistance which reached 65% of control value, and which, during continuous bathing with salicylic acid in HCl, rose slowly toward control level. Atropine SO 4 (0.2 mg kg −1 ) did not prevent or diminish the fall in resistance. There was no change in resistance when the mucosal barrier was broken by bathing the mucosa with 30 mM salicylic acid at pH 2.2, but the resistance fell immediately when that solution was replaced with 160 mN HCl. Back-diffusion of acid was, therefore, the proximate cause of vasodilatation. Close intraarterial infusion of histamine (1–360 ng ml blood −1 ) caused dose-related vasodilatation which was partially blocked by previous intravenous injection of pyrilamine maleate (1 mg kg −1 , repeated at 45 min) plus cimetidine (4 mg kg −1 , loading plus 1.4 mg kg −1 hr −1 continuous infusion). Rate of back diffusion of H + into the mucosa, calculated from measured A-V [H + ] and the base-excess curve for dog blood, was 35 μmol min −1 100 g −1 with 160 mN HCl and approximately 147 μmol min −1 100 g −1 with salicylic acid in HCl bathing the mucosa. Close intraarterial infusion of HCl at rates ranging from 0.2 to 3,288 nmol ml blood −1 caused roughly dose-related vasodilatation that was not blocked by pyrilamine plus cimetidine.

Central and Renal Circulation, Renin and Aldosterone in Plasma during Prazosin Treatment in Essential Hypertension

ABSTRACT The hemodynamic adaptation and the change in the renin‐aldosterone system during treatment with a new vasodilating drug, prazosin (Peripress®), were studied in 14 patients with essential hypertension before and after 2 and 4 months of treatment. The mean daily dose was 2 mg/day for the first 2 months and was increased individually up to 7.0 mg/day during the last 2 months in those patients whose mean arterial blood pressure (MAP) remained elevated. The reduction of MAP was mainly due to a decline in peripheral resistance, but also to a decrease in cardiac output in 4 of the patients. Effective renal plasma flow increased from 220 to 254 ml/min m2, probably as a result of a fall in vascular resistance in the kidneys. The plasma volume showed a small, transient increase after 2 months, from 19.0 to 20.0 ml/cm body height, whereas pulmonary plasma volume was unchanged, indicating a slight redistribution of plasma between the pulmonary and the systemic circulation. Body weight increased from 75.1 to 77.1 kg which, although a crude parameter, might indicate volume expansion. Plasma renin activity showed a small, transient increase after 2 months, from 0.46 to 0.65 nmol A1/I h, whereas plasma aldosterone concentration was unchanged, indicating that a volume expansion was not a result of a stimulated renin‐aldosterone system. The serum sodium and chloride concentrations fell from 142.7 to 140.2 mmol/l and from 105.9 to 103.1 mmol/***l, respectively.

Participation of beta receptors in reflex vasodilatation in the dog.

The effects of propranolol, given by direct intraarterial injection, on the reflex vasodilatation induced in the atropinized isolated gracilis muscle by rapid intravenous administration of norepinephrine, were studied in dogs. In these studies, both atropine and atropine plus propranolol did not significantly alter the maximum fall in vascular resistance in the perfused gracilis muscle following intravenous norepinephrine; however, if the reflex responses were evaluated as integrated areas of vasodilatation, atropine attenuated the vasodilatation and the administration of propranolol further attenuated the reflex. In fact, the value of the integrated areas of vasodilatation was 52.8 +/- 9 mmHg/min in the basal state, 39 +/- 6 mmHg/min after administration of atropine, and 24 +/- 7 mmHg/min after propranolol, whereas the integrated areas of the systemic hypertension did not show any modification. These results prompt us to conclude that the adrenergic beta receptors participate in the reflex vasodilatation, although the mechanism of their action needs further elucidation.

Drug-induced changes in capillary filtration coefficient and blood flow in the innervated small intestine of the anaesthetized cat.

1 A modification of the Folkow Technique for simultaneous measurement of blood flow and capillary filtration coefficient (CFC) in the cat jejunum is described. The modification retained the sympathetic innervation of the preparation, and in the present experiments, drugs were administered intravenously.2 There is evidence that CFC is a cardiovascular quantity independent of blood flow or regional vascular resistance in these preparations. Low doses of drugs may affect CFC without altering the blood pressure, blood flow, or heart rate.3 Under control conditions the CFC, a measure of functional exchange vessel area, was lower than previously reported for similar, but denervated preparations.4 alpha-Adrenoceptor stimulation with phenylephrine (1.0 mug kg(-1) min(-1), i.v.) caused a fall of 75-85% from control values of CFC with concomitant rises in blood pressure of 0-15% and falls in blood flow of 10-40%. The heart rate rose by 0-15%. Phentolamine (0.5-2.0 mg/kg, i.v.) caused a rise in CFC and a slight fall in vascular resistance, and blocked the effects of phenylephrine on this tissue.5 beta-Adrenoceptor stimulation with isoprenaline (0.2 mug kg(-1) min(-1), i.v.) caused a rise in CFC of 75-110%, a fall in blood pressure of 0-10%, a rise in blood flow of 10-60% and a rise in heart rate of up to 35%. Propranolol caused a transient rise in CFC when injected i.v. in a dose of 0.1 mg/kg, which was adequate to block the effects of isoprenaline.6 Angiotensin (25-100 ng kg(-1) min(-1), i.v.) caused falls in CFC of up to 100% and rises in vascular resistance. Aminophylline (0.2-0.4 mg kg(-1) min(-1), i.v.) caused rises in CFC of up to 200% with falls in vascular resistance.7 Histamine (0.01 to 1.0 mug kg(-1) min(-1), i.v.) had little effect on vascular resistance, but 10 and 40 mug kg(-1) min(-1) caused falls in vascular resistance. Doses up to and including 10 mug kg(-1) min(-1) caused falls in CFC, but the higher doses, or smaller doses after histaminase inhibition caused rises in CFC. alpha-Adrenoceptor blockade reversed the fall in CFC caused by small doses of histamine, to a rise. Mepyramine completely blocked the effects of histamine on these preparations.8 5-Hydroxytryptamine (33-100 mug kg(-1) min(-1), i.v.) caused a rise in vascular resistance and a fall in CFC of up to 85%. These effects were blocked by methysergide (250 mug/kg, i.v.).9 Rises in CFC indicate an increase in functional exchange vessel area in the tissue, and falls in CFC a decrease in the area available for vascular exchange. These changes are examined against the possibility of the drugs causing reflex adjustments in sympathetic tone, of systemic deactivation of intravenously administered drugs, and of drug effects on vascular permeability.

Effect of acute isovolemic anemia on cardiac output and estimated hepatic blood flow in the conscious dog.

The effect of acute isovolemic anemia induced by Dextran 70 exchange (40 ml/kg body weight) on estimated hepatic blood flow, cardiac output, and related variables was studied in 27 experiments on 24 unsedated dogs. Experiments were performed 5-10 days after implantation of an electromagnetic flow transducer around the aorta and catheters in the hepatic vein, jugular vein, and carotid artery. Bromsulphalein infusion was used to measure estimated hepatic blood flows, and electromagnetic measurements of stroke volume and cardiac output were calibrated using a simultaneous dye-dilution curve. With a mean fall in hematocrit from 34.8 to 17.0 ml/100 ml, estimated hepatic blood flow rose from 53.6 ± 15.3 (SD) to 76.3 ± 21.1 ml/min kg -1 and splanchnic vascular resistance fell from 119 ± 41 to 93 ± 38 mm Hg/liter min -1 ( P <0.01). These changes were proportionately smaller than the increase in cardiac output (182 ± 80 to 350 ± 146 ml/min kg -1 ) and the fall in systemic vascular resistance (37.0 ± 4.9 to 21.7 ± 4.9 mm Hg/liter min -1 ), leading to a fall in the ratio of estimated hepatic blood flow to cardiac output from 34.3 to 25.7%. Bromsulphalein extraction ratio was significantly decreased, but Bromsulphalein clearance increased 44%. Splanchnic oxygen consumption did not change. β-receptor blockade in 6 dogs (propranolol 0.5 mg/kg body weight) failed to prevent or attenuate the increase in estimated hepatic blood flow or cardiac output when the blocking agent was given before induction of acute isovolemic anemia. Sixty minutes after accomplishment of anemia, estimated hepatic blood flow and cardiac output had returned toward but not to control levels. Induction of β-receptor blockade in the anemic dog did not influence the effects of time on estimated hepatic blood flow or cardiac output. We concluded that acute isovolemic anemia leads to a significant increase in estimated hepatic blood flow that is essentially independent of β-receptor stimulation.

Autonomic innervation of the pulmonary vascular bed in a toad ( Bufo marinus)

1. 1. Effects of nerve stimulation on pulmonary vascular perfusion pressure in saline-perfused is isolated lungs of Bufo marinus were studied. 2. 2. Evidence is presented that contraction of pulmonary visceral muscle may increase pulmonary vascular resistance. However, there is a separate musculature, as yet not located, of the vascular bed. 3. 3. The pulmonary vascular muscle is innervated by vagal cholinergic constrictor fibres and by sympathetic adrenergic dilator fibres. 4. 4. Non-adrenergic, non-cholinergic fibres in the vagus nerve cause a fall in vascular resistance but this may be an indirect effect of relaxation of visceral muscle. 5. 5. Two stages in the evolution of the autonomic nervous system are proposed.

Observations on the control of cerebral blood flow in the sheep fetus and newborn lamb.

Cerebral blood flow was measured with xenon 133 in 21 fetal sheep and 14 newborn lambs under 48 hours old. When the ewe breathed air, the average gray matter blood flow in the fetuses was 70.6 ml/100 g/min, the average white matter blood flow 15.4 ml/100 g/min and average gray matter oxygen consumption 2.06 ml/100 g/min. The corresponding values in the newborn lambs were 87.2, 17.8, and 2.98 ml/100 g/min. A reduction of fetal Pao 2 by 7 to 11 mm Hg at a constant Paco 2 or an increase of Paco 2 at constant Pao 2 caused a rise in blood flow and arterial pressure and a fall in vascular resistance. Intravenous catecholamines caused variable changes in blood flow but no significant change in gray matter oxygen consumption. Occlusion of the umbilical cord caused an average increase in gray matter blood flow of 50% of control, in white matter blood flow of 30%, and in gray matter oxygen consumption of 90%. By the end of the first hour, these values had fallen and were then similar to those seen in the newborn lamb. These changes were not seen in fetuses in which both vagi had been cut nor in two fetuses with a failing circulation.

Observations on the extrinsic neural control of cerebral blood flow in the baboon.

Cerebral blood flow was measured using 133 xenon in forty-five baboons lightly anesthetized with pentobarbital. Blood flow varied between 62 and 82 ml/100g/min in gray matter and between 15 and 21 ml/100g/min in white matter. Hypercapnia and hypoxia caused a rise in blood flow and a fall in vascular resistance. Blood flow was independent of mean arterial blood pressure over the range 60 to 130 mm Hg. Section of the cervical sympathetic nerve enhanced the vascular response to CO 2 . Stimulation of the sympathetic nerve caused a reduction in blood flow in proportion to the initial blood flow. Similarly, after sympathectomy, blood flow was uniformly higher than control over the range of Pa o 2 tested (35 to 450 mm Hg). After sympathectomy, blood flow was little different from control at low blood pressure but was higher within the physiological range and blood flow then fell steadily as pressure was reduced. When the carotid, vagus, and aortic nerves were cut in the neck, the blood flow response to hypoxia and hypercapnia was reduced, and when the aortic or vagus nerves were stimulated centrally, blood flow increased independently of Pa CO 2 . Section of the seventh cranial nerve caused small and variable changes in blood flow, but if the vagus nerves had previously been sectioned, stimulation of the seventh cranial nerve caused an increase in blood flow in some of the tests. These results indicate that cerebral blood vessels are under reflex control. Possible receptors and pathways involved are discussed.

Action of bradykinin on human pulmonary circulation. Observations in patients with mitral valvular disease.

Twenty-one patients with pulmonary hypertension secondary to rheumatic mitral valve disease were submitted to right and left heart catheterization and received a continuous intravenous infusion of synthetic bradykinin (average dose, 0.98 µg/kg/min). The drug elicited an appreciable fall of the systemic vascular resistance simultaneously with a decrease of the mean systemic arterial pressure and an increase of the cardiac output in all cases. The rise in cardiac output derived mainly from an increase in heart rate, since the modifications of the stroke volume were generally of low magnitude. In the pulmonary circulation, the increase in blood flow was coincident with a rise of the mean arterial and venous (left atrial) pressures in 19 and all patients, respectively. The pulmonary vascular resistance fell in 19 patients, but no appreciable modifications were noted in pulmonary blood volume. The changes in the lesser circulation were interpreted as expressing secondary effects, either mechanical or reflex, consequent to the action of bradykinin on the systemic vessels and heart rather than a direct effect of the drug on the pulmonary vessels.

Factors controlling pulmonary vascular resistance in fetal lambs

A series of experiments measuring pulmonary vascular resistance in the fetal lamb revealed that spontaneous changes in resistance occur in the unexpanded fetal lung; expansion of the fetal lung with a gas mixture that produces no significant alteration in arterial pO₂ or pCO₂ results in a marked fall in pulmonary vascular resistance; expansion of fetal lungs with deoxygenated dextran in saline produces only a small fall in pulmonary vascular resistance; inflation of fetal lungs with oxygenated dextran in saline and arterial blood produces a marked fall in vascular resistance; the fall in pulmonary vascular resistance with air inflation of the fetal lung cannot be ablated by vagotomy, atropinization, or administration of ismeline.

SODIUM, POTASSIUM, AND PERIPHERAL RESISTANCE IN THE RAT TAIL.

The early effects of systematic changes of environmental Na + on vascular resistance and on cationic equilibration were studied using a closed circuit perfusion of the rat tail. The recirculating medium was monitored for Na + and K + with glass electrodes operating through a computer. The composition of a given medium perfusing the vascular bed is very rapidly altered as it comes into equilibrium with cells and interstitial tissue. Because exchanges begin quickly, only limited conclusions can be drawn from manipulation of a perfusing medium without close monitoring of the equilibration process. Reduction of sodium in the medium, using sucrose as osmotic replacement, is followed by a rapid efflux of Na + , some of which apparently comes from cells. This is associated with a fall of vascular resistance. Neither efflux nor fall in resistance occurs if choline or K + is used as replacement for Na + . Elevation of potassium in the medium is followed by a gradual fall during equilibration of the ion and, if K + is raised sufficiently, an increase in vascular resistance occurs. These findings support the view that the transcellular distribution of Na + and K + is causally involved in the maintenance of vascular tone.

Pressure-flow relationships in the perfused dog spleen.

Isolated and nonisolated preparations of dog spleens were perfused at various rates by means of a blood pump inserted proximal to the splenic artery. Pressures were measured continuously and vascular resistances were calculated. In both preparations vascular resistance decreased as perfusion pressure gradient increased over a wide range (67–313 mm Hg). Pressures and resistances were consistently lower at each perfusion rate in the isolated preparations, presumably due to periarterial nerve transection. The data suggest that the fall in vascular resistance is primarily brought about by a passive opening of closed channels and a further distention of open vessels unrelated to neurogenic factors. There is no evidence that the smooth muscle of the perfused splenic vascular bed actively contracts as flow and pressure increase.