Priority of blood flow to splanchnic organs in humans during pre- and post-meal exercise

Cardiac output and superior mesenteric arterial flow in five healthy young men were followed using Doppler ultrasound techniques at rest and during 4 min bouts of bicycle exercise in both a pre- and a post-meal situation. The meal given was mixed and heavy, with an energy content (related to body size) of about 1400–1600 kcal (5.9-6.9 MJ). Two levels of exercise, 50–65 W and 150–200 W (about 75% of Vo_tmax), were tested, with the subjects cycling in a reclining position. Superior mesenteric arterial flow increased threefold, to about 1.11 min^-1, after the meal. During exercise in the fasting situation there were only modest changes in splanchnic vascular conductance, and moderate increases in superior mesenteric arterial flow were actually recorded. Exercise in the post-prandial state caused appreciable reductions in splanchnic vascular conductance, and a 38% reduction was observed during the most heavy exercise. However, not even such a decrease in conductance resulted in any definite reduction in superior mesenteric arterial blood flow, which was maintained at the pre-exercise level. Cardiac output increased by about 1.3 1 min^-1 after the meal. The exercise-induced increases in cardiac output were of the same order in the fasting and in the post-prandial state. Variance analyses showed the high cardiac output levels reached during postprandial exercise to be no different from levels that would be reached by pure summation of the changes caused by eating alone and by exercise alone. It is concluded that blood flow to the splanchnic organs in reclining man retains its high pre- and post-prandial priority during short exercise bouts of up to 75% of Vo_Smax.     

Uterotrophic effect of a saturated fatty acid 17-ester of estradiol-17beta administered orally to juvenile rats

In comparison to estradiol-17beta, the naturally synthesized estradiol-17beta-17-fatty acid esters are potent estrogens when administered subcutaneously. A lipophilic character of estradiol-17-esters could partially protect them from metabolic inactivation. In order to compare their relative estrogenic potency when administered orally, the uterotrophic response to different dosages (0, 2.5, 25, 250 and 2500 nmol/kg BW/day) of estradiol-17beta and estradiol-17beta-17-stearate was assessed in juvenile Sprague-Dawley female rats. Estrogens were administered by oral gavage once a day for 6 days. On the 7th day uterus and vagina were dissected, weighed, and examined microscopically. At 2.5 and 25 nmol/kg BW/day, no difference was detected in the uterus weight compared to control animals which received the vehicle alone (corn oil). At 250 nmol/kg BW/day, the uterotrophic response was maximal in estradiol-17beta-17-stearate-treated animals (x2.40-2.70), whereas it was moderate in estradiol-17beta-treated rats (x1.86) at the same dosage. This differential weight gain effect of estradiol-17beta-17-stearate was correlated with typical microscopic changes in uterus and vagina. The results are in favour of a stronger estrogenic effect of orally given lipoidal estrogens compared to estradiol-17beta. This could be explained by a slower but sustained absorption of estradiol-17beta released from estradiol-17beta-17-stearate by esterases and/or by a facilitated transfer of esters in the lymphatic circulation.     

Peripheral blood flows during colorectal distension in anaesthetised dogs

Distension of the descending colon elicits reflex cardiovascular responses, including increases in heart rate and arterial blood pressure. To study the relative contribution of vasoconstriction in individual vascular beds to this reflex response, experiments were performed on seven dogs anaesthetised with chloralose and instrumented with electromagnetic flowmeters around the superior mesenteric, the left renal and the left external iliac arteries. The colorectal portion of the intestine was distended at constant pressure (36.6 mm Hg, 4.9 kPa mean; range 25–50 mm Hg, 3.3–6.7 kPa) with warm Ringer solution for periods of 2 min. After a set of control distensions, the experiments were performed whilst the reflex rise in arterial pressure was prevented by removal of blood from the arterial tree. In control distensions arterial pressure increased by 11.3±1.5 mm Hg, 1.51±0.12 kPa (mean±SEM). In distensions at constant arterial pressure, peripheral blood flows were altered to different extents in the three territories studied: vascular resistance increased by 30.8±5.6% (P<0.01) in the mesenteric, by 4.1±1.5% (P<0.03) in the renal, and by 15.2±6.8% (NS) in the external iliac bed. We conclude that colorectal distension may reflect activation of a function-specific pathway of the sympathetic nervous system, which leads to much greater vasoconstriction in the splanchnic circulation than in renal or musculocutaneous circulations.     

Hypoxic pulmonary vasoconstriction is heterogeneously distributed in the prone dog

Hypoxic pulmonary vasoconstriction (HPV) is thought to protect gas exchange by decreasing perfusion to hypoxic regions. However, with global hypoxia, non-uniformity in HPV may cause over-perfusion to some regions, leading to high-altitude pulmonary edema. To quantify the spatial distribution of HPV and regional PO2 (PRO2) among small lung regions (approximately 2.0 cm3), five prone beagles (approximately 8.3 kg) were anesthetized and ventilated (PEEP approximately 2 cm H2O) with an F1O2 of 0.21, then 0.50, 0.18, 0.15, and 0.12 in random order. Regional blood perfusion (Q), ventilation (VA) and calculated PRO2 were obtained using iv infusion of 15 microm and inhalation of 1 microm fluorescent microspheres. Lung pieces were clustered by their relative blood flow response to each F1O2. Clusters were shown to be spatially grouped within animals and across animals. Lung piece resistance increased as PRO2 decreased to 60-70 mmHg but dropped at PRO2's < 60mmHg. Regional ventilation changed little with hypoxia. HPV varied more in strength of response, rather than PRO2 response threshold. In initially homogeneous VA/Q lungs, we conclude that HPV response is heterogeneous and spatially clustered.     

Thinning of fetal pulmonary arterial wall and postnatal remodelling: Ultrastructural studies on the respiratory unit arteries of the pig

Summary Adaptation to extra-uterine life and postnatal remodelling of intra-acinar arteries was followed in 34 Large White pigs, from birth to adult life, applying morphometry to light and electronmicroscopic studies. After birth, percentage wall thickness decreased rapidly due to a reduction in overlap of adjacent smooth muscle cells and an increase in smooth muscle cell surface area/volume ratio, (p<0.01 at 12 h), without a reduction in the volume density of smooth muscle cells. Smooth muscle cells appeared immature at birth and synthetic rather than contractile organelles predominated. Between 3 weeks and 6 months myofilament volume density doubled (p< 0.0001). At all ages, pericytes, intermediate and smooth muscle cells showed similar volume densities of contractile and synthetic organelles. Thus, the high fetal pulmonary vascular resistance appeared to be due to the shape and arrangement of smooth muscle and other contractile cells within the vessel wall, rather than an excessive contractility of these cells. After birth rapid remodelling of arterial wall structure achieved a reduction in wall thickness by 30 min, continuing during the first week of life. After 3 weeks, remodelling involved an increase in wall thickness, connective tissue deposition with more collagen than elastin (p<0.0001), and smooth muscle cell differentiation.     

Nitric oxide mediates intestinal hyperaemic responses to intraluminal bile-oleate

It has long been recognized that intestinal blood flow increases at mealtimes. Mesenteric hyperaemia is also evoked by activation of sensory peptidergic nerves. Our studies explored the possible role of endogenous nitric oxide (NO) in the rat intestinal vasodilator response to luminal instillation of an oleic acid plus bile mixture before and after acute intrajejunal instillation of capsaicin and after chronic pretreatment with capsaicin. In anaesthetized rats we measured jejunal blood flow (BF) with an ultrasonic Doppler flowmeter and systemic arterial pressure (AP) with a pressure transducer. Intestinal perfusion with 80 mM oleic acid in bile increased BF by 98±12%. Instillation of 4 mg of capsaicin into the jejunal lumen initially increased BF by 42±9% but was followed by vasoconstriction. Inhibition of NO synthase with 25 mg/kg i.v. N-nitro-L-arginine (L-NNA) decreased BF by 27±5% and increased AP by 37±11%. After treatment with L-NNA and after acute and chronic administration of capsaicin, the bile-oleate-induced maximal increases in BF above control levels were 42±7%, 65±12%, and 58±8%, respectively. The observed inhibitory effect of L-NNA on the intestinal hyperaemic response to the bile-oleate mixture was reversed by pretreatment with L-arginine (100 mg/kg i.V.). In capsaicin pretreated rats the subsequent bile-oleate-induced hyperaemia was reduced in magnitude but the inhibitory effects of L-NNA were proportionately the same as in animals not receiving capsaicin. These findings support the hypothesis that NO is involved with bile-oleate-induced mesenteric hyperaemia.     

Effect of ornid on regulation of the cerebral circulation

An investigation by radioisotope, electromagnetic, and resistographic methods showed that Ornid reduces the cerebral blood flow. At the same time it completely inhibits constrictor reactions of the cerebral vessels to stimulation of sympathetic and somatic nerves. Ornid also has a protective action against experimental disturbances of the cerebral circulation of adrenergic nature.Laboratory of Pharmacology of the Nervous System, Institute of Pharmacology, Academy of Medical Sciences of the USSR, Moscow. (Presented by Academician of the Academy of Medical Sciences of the USSR V. V. Zakusov.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 87, No. 5, pp. 427–429, May 1979.     

Minimum realisations and modelling of biological systems

A state variable model in the canonical form of Bucy is constructed from the given impulse response of a finite-dimensional, discrete-time, linear constant dynamical biological (arterial circulatory) system.     

Hydrogen peroxide-induced Ca responses in CNS pericytes

Objective: The aims of the present study were to elucidate the interaction of reactive oxygen species (ROS) and Ca²⁺ response in central nervous system (CNS) pericytes. Methods: The intracellular Ca²⁺ concentration was measured using fluorescent Ca²⁺ indicator, fura-2, in cultured CNS pericytes. Results: Hydrogen peroxide evoked a dose-dependent increase in cytosolic Ca²⁺, which was completely inhibited by catalase. Removal of external Ca²⁺ or addition of nicardipine (1 μM) during application of hydrogen peroxide did not affect Ca²⁺ response. Incubation of the cells in Ca²⁺ free solution did not abolish but slightly reduced Ca²⁺ response by hydrogen peroxide. Ca²⁺ response to hydrogen peroxide was not altered by the depletion of intracellular Ca²⁺ by thapsigargin (1 μM). Pretreatment of the cells with tyrosine kinase inhibitor genistein (100 μM) or tyrphostin A47 (30 μM) significantly reduced Ca²⁺ increase by hydrogen peroxide. Conclusions: These results indicate that hydrogen peroxide evokes Ca²⁺ increase predominantly by release from intracellular Ca²⁺ store, which may be regulated by tyrosine kinases.