Biomedical subjects

H G Bohlen

Publications and source records attributed to H G Bohlen.

At least 19 recordsLinked to original sources

PubMed1996

Intestinal absorption of sodium and nitric oxide-dependent vasodilation interact to dominate resting vascular resistance.

The villi of the small intestine maintain a hypertonic interstitium at all times, and the submucosal glands constantly secrete ions and accompanying water into the lumen. Generation of the 400- to 600-mOsm interstitial fluid in the villus and secretion by glands may require a large expenditure of energy and, consequently, have major effects on intestinal vascular regulation to supply oxygen and nutrients. Blood flow and oxygen consumption were measured in the ileum of anesthetized rats during natural resting conditions with physiological sodium chloride in the bathing fluid and during isosmotic replacement of sodium chloride with mannitol. Microvascular pressures and blood flow were used to determine the changes in resistance of the major arterioles and the terminal vasculature. When mannitol replaced sodium chloride in contact with the villi, intestinal blood flow decreased to 58.6 +/- 2.8% of control, and oxygen consumption was 54.2 +/- 3.4% of control. Resistance of the major arterioles increased 101.7 +/- 9.9%, and that of the terminal vasculature increased 40.4 +/- 6.2%. The increased resistance appeared to be caused by suppression of a nitric oxide mechanism. Local application of 10(-4) mol/L NG-nitro-L-arginine methyl ester caused about the same reduction in flow and increases in regional vascular resistance as during replacement of sodium but did not alter the oxygen consumption. These data indicate that about half of the intestinal metabolic rate during natural resting conditions is devoted to sodium secretion/absorption. Large resistance vessels are dilated to maintain a high blood flow through release of nitric oxide. We propose that dilation of the terminal vasculature in the metabolically active tissues increased flow velocity sufficiently in the major resistance vessels to cause a flow-mediated release of nitric oxide.

Animals↗

PubMed1995

Vascular endothelium and smooth muscle remodeling accompanies hypertrophy of intestinal arterioles in streptozotocin diabetic rats.

The purpose of this study was to document alterations in endothelial and smooth muscle cell morphology of first- and second-order intestinal arterioles after 6 months of streptozotocin-induced diabetes. Both light and scanning electron microscopic techniques were used to quantitate the changes in the microvasculature. After rendering the first- and second-order intestinal arterioles passive and processing the vessels, it was determined that these microvessels were significantly dilated in the diabetic animals. Further examination revealed that in the diabetic animals, the cross-sectional area of the endothelial layer was increased in both 1A and 2A vessels, and the smooth muscle layer cross-sectional area was significantly increased in 1A vessels. Individual smooth muscle cells were significantly increased in width in the diabetic animals, but not in length. These data suggest that in this model of diabetes in rats, intestinal arteriolar hypertrophy was accompanied by significant remodeling of the arteriolar wall.

Animals↗

PubMed1995

Endothelial-dependent vasodilation is preserved in non-insulin-dependent Zucker fatty diabetic rats.

Alterations in the structural properties of the microvasculature and in vasodilation mediated by endothelial- and, to some extent, nonendothelial-dependent mechanisms occurs in insulin-dependent diabetic humans and animals. Less severe problems of this type appear to occur during non-insulin-dependent diabetes mellitus (NIDDM) in humans, but data based on animal models of NIDDM are not available. The endothelial- and nonendothelial-mediated dilation of intestinal arterioles was studied in insulin-resistant male Zucker fatty diabetic (DB) rats and their lean normal male littermates (LM) at ages 22-25 and 35-40 wk. DB become hyperglycemic (450-550 mg/100 ml) at age 9-10 wk. Microiontophoretic release of acetylcholine, ADP, and nitroprusside onto arterioles caused equivalent dilation in LM and DB for both large and intermediate diameter arterioles. Administration of streptozotocin (STZ) to DB at age 18-19 wk lowered their insulin concentration approximately 25% but did not significantly effect the resting plasma glucose concentration. However, endothelial-dependent vasodilation was attenuated by 70-80% within 8-10 wk. The overall results indicate that prolonged hyperglycemia in insulin-resistant but hyperinsulinemic rats does not impair the endothelial- and nonendothelial-dependent dilation of the intestinal microvasculature. However, compromising beta-cell function with STZ, as indicated by lowering the insulin concentration by one-fourth, substantially compromises endothelial-dependent dilation similar to that found in insulin-dependent diabetic rats and humans.

Acetylcholine↗

PubMed1995

Resting oxygenation of rat and rabbit intestine: arteriolar and capillary contributions.

Counter-current exchange of oxygen may occur between inflow and outflow microvessels of the small intestine and greatly influence the dominant sites of tissue oxygenation. To determine the location and magnitude of potential exchange, percent saturation of hemoglobin with oxygen (%SHb) was measured in microvessels throughout the intestine of rats and rabbits. Oxygen losses from systemic arterial blood through large and intermediate arterioles (second order, 2A) was 5-7%SHb in both species, and there was no evidence of an increase in percent saturation along intermediate and large venules. A larger loss of oxygen from arterioles and an increase in venous saturation would be evident if significant arteriolar to venular counter-current exchange of oxygen occurred in the submucosa. From 2A to the villus tip, arteriolar saturation decreased approximately 10%SHb in rabbits and approximately 15%SHb in rats; the villus tip percent saturation was 72.9 +/- 3.9%SHb in rabbits and 69.9 +/- 2.9%SHb in rats. An additional decrease of 5%SHb in rabbits and 15%SHb in rats occurred across the villus capillaries and smallest venules. Although the total reduction in percent saturation across the villi was different between the two species, 70-90% of the total arteriovenous oxygen losses occurred in the capillaries and small arterioles of the villi. We found no evidence of counter-current exchange of oxygen in villi or any other vascular region. Rather, as appears to occur in most organs, small arterioles in conjunction with capillaries dominate resting oxygen exchange to tissue.

Animals↗

PubMed1995

Excess oxygen delivery during muscle contractions in spontaneously hypertensive rats.

These experiments determined whether a deficit in oxygen supply relative to demand could account for the sustained decrease in tissue PO2 observed during contractions of the spinotrapezius muscle in spontaneously hypertensive rats (SHR). Relative changes in blood flow were determined from measurements of vessel diameter and red blood cell velocity. Venular hemoglobin oxygen saturation measurements were performed by using in vivo spectrophotometric techniques. The relative dilation [times control (xCT)] of arteriolar vessels during contractions was as large or greater in SHR than in normotensive rats (Wistar-Kyoto), as were the increases in blood flow (2 Hz, 3.50 +/- 0.69 vs. 3.00 +/- 1.05 xCT; 4 Hz, 10.20 +/- 3.06 vs. 9.00 +/- 1.48 xCT; 8 Hz, 16.40 +/- 3.95 vs. 10.70 +/- 2.48 xCT). Venular hemoglobin oxygen saturation was lower in the resting muscle of SHR than of Wistar-Kyoto rats (31.0 +/= 3.0 vs. 43.0 +/- 1.9%) but was higher in SHR after 4- and 8-Hz contractions (4 Hz, 52.0 +/- 4.8 vs. 43.0 +/- 3.6%; 8 Hz, 51.0 +/- 4.6 vs. 41.0 +/- 3.6%). Therefore, an excess in oxygen delivery occurs relative to oxygen use during muscle contractions in SHR. The previous and current results can be reconciled by considering the possibility that oxygen exchange is limited in SHR by a decrease in anatomic or perfused capillary density, arteriovenular shunting of blood, or decreased transit time of red blood cells through exchange vessels.

Animals↗

PubMed1994

Role of a lymphatic system in glucose absorption and the accompanying microvascular hyperemia.

In this study we evaluated the importance of a functional intestinal lymphatic system on changes in arteriolar and venular blood oxygen content, vasodilation, and elevation of venous blood osmolarity during glucose absorption. Glucose absorption was associated with a doubling of the arteriovenous oxygen difference [(A-V)O2], a 50 mosM increase in venous blood osmolarity, and 17% dilation of the intermediate-diameter arterioles. After the lymph vessels were mechanically blocked with mineral oil, glucose absorption again doubled the (A-V)O2, indicating that glucose was absorbed without a functional lymphatic system. Furthermore, venous blood osmolarity and arteriolar diameter increased similarly with and without a functional lymphatic system. This study indicates that even though the lymphatic system likely facilitates distribution of hypertonic material in the bowel wall during absorption, blockade of the lymphatics did not appreciably hinder vasodilation, glucose absorption, changes in intravascular oxygen content, or the elevation of tissue hyperosmolarity, as judged by the tonicity of the venular blood. Therefore, passage of materials absorbed or released in the mucosa to the submucosa through venular blood flow may be very important to the mechanism of absorptive hyperemia.

Animals↗

PubMed1994

Active and passive arteriolar regulation in spontaneously hypertensive rats.

This study determined to what extent active and passive wall tensions increase in in vivo intestinal arterioles of 13- to 15-week-old and 25- to 27-week-old spontaneously hypertensive rats (SHR) to maintain normal or smaller arteriolar diameters during microvascular hypertension. Acetylcholine and nitroprusside were used to determine whether vascular muscle relaxation to endothelium-derived relaxing factor or cyclic GMP is impaired. Large arterioles of hypertensive rats have passive tension-circumference relations that are steeper and shifted to the left compared with those of age-matched controls; passive resistance to distension limits vasodilation in hypertensive rats except at their naturally elevated arteriolar pressure. Passive tension contributes approximately 30% of the total resting tension in arterioles of hypertensive and normotensive rats because a greater passive tension occurs at the 20% to 25% constricted resting diameter in hypertensive rats. Absolute and relative changes in the diameter of SHR arterioles during acetylcholine and nitroprusside application were equal to or greater than those in Wistar-Kyoto rats. However, reduction in active tension was suppressed in older SHR and remained approximately 50% higher than that found in older Wistar-Kyoto rats during drug application. Vasoconstriction and increased passive resistance to distension of the arteriolar wall diminish the active tension required to maintain normal or smaller resting diameters against microvascular hypertension. However, the elevated microvascular pressure in hypertensive rats is required to allow near-normal dilation to compensate for their increased passive resistance to stretch and decreased ability to relax active tension through cyclic GMP mechanisms.

Acetylcholine↗

PubMed1993

Evaluation of carbocyanine-labeled erythrocytes for microvascular measurements.

Red blood cells labeled with the carbocyanine dyes, 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate (DiI) and 3,3'-dioctadecyloxacarbocyanine perchlorate (DiO), were evaluated for use in making microvascular measurements in rat small intestine and spinotrapezius muscle. We determined the minimum concentration of each dye which produced near maximal fluorescent intensity and labeled cell fraction. These dyes, which have excitation and emission spectra similar to fluorescein and rhodamine derivatives, have a number of advantages over the isothiocyanates: (1) the labeling procedure is quicker, easier, and less expensive; (2) the labeled cell fraction and the fluorescent intensity of DiI and DiO cells are stable for long periods of time in the rat circulation; and (3) DiI-labeled cells are brighter and transmit light through overlying erythrocytes better than rhodamine X isothiocyanate. However, in vitro and in vivo evaluations illustrate the potential limiting effects of vessel diameter and cell velocity on the accuracy of microvascular measurements made using this technique. In the small intestine and spinotrapezius muscle preparations, measurements of labeled cell flux were readily reproducible and could be partly automated with image analysis only in capillaries and small venules. Counting labeled cells in larger vessels by human observation or with automation was not reproducible, presumably due to absorption and dispersion of the fluorescent signal by overlying erythrocytes and smearing of the cell image at high cell velocities.

Animals↗

PubMed1993

Topical hyperglycemia rapidly suppresses EDRF-mediated vasodilation of normal rat arterioles.

Arteriolar dilation to endothelium-derived relaxing factor (EDRF) is suppressed early in diabetes mellitus. The purpose of this study was to determine whether acute exposure to a hyperglycemic media can suppress EDRF function of normal arterioles. Dilation of intestinal arterioles to iontophoretically applied acetylcholine (ACh) and nitroprusside was measured in normoglycemic rats before and after 1 h of topical exposure to isotonic solutions containing D-glucose concentrations of 200, 300, and 500 mg/100 ml. Exposure to a D-glucose concentration of 200 mg/100 ml had no effect on vasodilation to ACh. D-Glucose concentrations of both 300 and 500 mg/100 ml caused significant suppression of the responses: for example, at the approximate 50% effective dosage (100 nA), the dilatory response was decreased by 60% at a D-glucose concentration of 300 mg/100 ml and 55% at a D-glucose concentration of 500 mg/100 ml. Responses to nitroprusside were not significantly (P < 0.05) impaired after exposure to D-glucose concentrations of 200, 300, or 500 mg/100 ml. Exposure to an isotonic L-glucose concentration of 500 mg/100 ml for 1 h had no significant (P > 0.05) effect on responses to ACh. Pretreatment with superoxide dismutase, catalase, indomethacin, or meclofenamic acid preserved EDRF-mediated vasodilation during exposure to a D-glucose concentration of 500 mg/100 ml at almost all the ACh dosages tested. These results indicate that oxygen radicals formed in part by increased eicosanoid synthesis during exposure to D-glucose hyperglycemia interfere with the EDRF mechanism before its action on the microvascular smooth muscle.

Acetylcholine↗

PubMed1993

Sodium hyperosmolarity of intestinal lymph causes arteriolar vasodilation in part mediated by EDRF.

This study evaluated 1) the effect of increased submucosal lymph osmolarity on the regulation of first-order (1A) and second-order (2A) intestinal arterioles and 2) the role of endothelium-derived relaxing factor (EDRF) in hypertonic-induced vasodilation. Increasing the submucosal lymph osmolarity from 280 to 400 mosM, in increments of 30 mosM, resulted in a dose-dependent dilation of 1A and 2A. A submucosal lymph tonicity of 340 mosM, as occurs during glucose and oleic acid absorption, caused dilation of 1A (118%) and 2A (124%) equivalent to that during absorptive hyperemia. The dilation caused by 400 mosM mannitol (137%) was similar to that with 340 mosM NaCl (131%) and approximately 70% of that with 400 mosM NaCl (152%). After EDRF blockade, the responses to sodium hypertonicity decreased by about one-half; blockade reduced mannitol-induced dilation by 22%. These results indicate that sodium hypertonicity, as occurs during absorption, can play a major role in absorptive hyperemia, and about one-half of the dilation is related to a sodium-coupled release of EDRF.

Animals↗

PubMed1993

Adrenergic and pressure-dependent vascular regulation in sedentary and trained rats.

In this study, we determined if aerobic exercise training alters adrenergic or pressure-dependent vascular regulation in the rat hindlimb or intestine. Pressor responses to bilateral carotid artery occlusion and systemic phenylephrine (PE) infusion were not altered by training. During occlusion, peak and steady-state changes in hindlimb vascular resistance (HLR) were significantly greater in trained (24 and 13%) than in sedentary (8 and -3%) rats; a similar trend existed for intestinal vascular resistance (IR). The pressure-dependent contribution was consistent between groups (HLR: peak 55-85%, steady state 25-45%; IR: peak and steady state 40-65%). During PE infusion, increases in IR and HLR were similar between groups. The increase in HLR was substantially pressure dependent in both groups (approximately 50% at highest dose) as was the change in IR in trained rats. However, the IR response to PE was not pressure dependent in sedentary rats. The direct effects of PE were similar between sedentary and trained rats in the hindlimb but were suppressed in the intestine of trained rats compared with sedentary rats. Therefore, aerobic exercise training altered adrenergic and pressure-dependent vasoregulatory mechanisms in both skeletal muscle and intestinal tissues.

Animals↗

PubMed1992

Intestinal lymphatic vessels release endothelial-dependent vasodilators.

This study evaluated the possibility that the endothelial cells of microscopic lymphatic vessels can release vasoactive agents which affect the lymphatic vessels and nearby arterioles. Microinotophoresis of acetylcholine (ACh) or bradykinin (BK) onto the wall of quiescent submucosal lymphatic vessels in the rat small intestine had no discernible effects on their diameters but caused spontaneously active mesenteric lymphatic vessels to constrict. Application of ACh or BK to the arteriolar wall caused significant vasodilation. Release of either drug onto the wall of a nearby lymphatic produced arteriolar dilation that was approximately 80% of that observed with direct application to the arteriolar wall; drug application into parenchymal tissue produced a dilation less than 25% of that observed during application to the lymphatic. NG-monomethyl-L-arginine application to the lymphatic blocked all ACh-induced lymphatic-mediated responses but had no effect on the response to direct ACh application to the arteriolar wall or any of the responses to BK application. These results are consistent with the hypothesis that lymphatic endothelial cells are capable of releasing agents that dilate nearby arterioles and cause spontaneously active lymphatic vessels to constrict.

Acetylcholine↗

PubMed1992

Functional adaptations of rat skeletal muscle arterioles to aerobic exercise training.

This study tested the hypothesis that both structural and functional adaptations of arterioles occur within the skeletal muscle of rats aerobically trained for 8-10 wk with treadmill exercise. The training regimen used has been shown to elicit a 37% increase in plantaris citrate synthase activity but did not result in an elevation in citrate synthase activity in the spinotrapezius or gracilis muscles of rats used in this study. In the in vivo resting spinotrapezius muscle, arteriole diameters were similar in sedentary (SED) and trained (TR) rats. However, large- (1A) and intermediate- (2A) sized arterioles dilated proportionately more in TR than in SED rats during 1- to 8-Hz muscle contractions, even though the passive mechanical properties (circumference-passive wall tension relationships) were similar between groups. Vascular casts demonstrated a trend for an increase in the number of small (3A) arterioles and an approximately 20% increase in the passive diameter of 1A and 2A arterioles in the spinotrapezius muscle of TR rats. In contrast, in the gracilis muscle, arteriole diameters and density were identical in SED and TR rats, but the capillary-to-muscle fiber ratio was approximately 15% higher in TR rats. The results suggest that aerobic exercise training can greatly increase functional vasodilation and induce a slight increase in vascular density in skeletal muscle tissues, even if the oxidative capacity of these tissues is not increased by the training regimen.

Adaptation, Physiological↗

PubMed1991

Vascular smooth muscle structure and juvenile growth in rat intestinal venules.

The morphological structure of individual vascular smooth muscle cells from intestinal venules was evaluated with a combination of quantitative scanning (SEM) and transmission (TEM) electron microscopy techniques. In addition, growth of individual venular smooth muscle cells and of the overall vessel wall was compared from measurements of these variables during the rapid juvenile growth spurt from ages 4 to 6 and 10 to 12 weeks in Wistar-Kyoto rats. SEM revealed that smooth muscle cells of intestinal venules in weanling rats are very long (379 +/- 91 [SD] microns) and wide (6.0 +/- 1.3 microns) and very little further cell enlargement occurs during rapid juvenile growth. TEM studies indicated that passive inner vessel diameter and total muscle layer cross-sectional area of both the largest and intermediate diameter venules of young rats, as well as the percentage of the total wall area as muscle tissue in each venule type, did not significantly increase during body growth. These observations indicate that both the intestinal venules and their smooth muscle cells reach mature dimensions at a very early stage of life. Comparison of intestinal vascular smooth muscle cell dimensions indicates that venular smooth muscle cells are much larger in both cell length and volume than comparable arteriolar smooth muscle cells.

Aging↗

PubMed1991

Hepatic venular pressures of rats, dogs, and rabbits.

We tested the hypotheses that the hepatic venule pressures (Phv), just downstream from the hepatic sinusoids, are closely similar (less than 2 mmHg) either to the portal venous pressure (Ppv), indicating a high hepatic venous resistance, or to the inferior vena cava (Pivc) pressure, indicating a high portal-sinusoidal venous resistance, as reported by previous investigators. A micropipette servo-null pressure measurement technique was used with rats, dogs, and rabbits. Phv, referred to the anatomic level of the vena cava, averaged 5.1 +/- 1.0, 6.4 +/- 1.1, and 5.4 +/- 1.0 (SD) mmHg in the rats, puppies, and rabbits, respectively. Ppv averaged 8.0 +/- 1.4, 10.8 +/- 2.2, and 7.4 +/- 1.5 mmHg, respectively. Norepinephrine infusion into the portal vein (1-5 micrograms.min-1.kg-1) caused Ppv to increase and the portal venous flow to decrease but did not significantly affect Phv. The hepatic venous circuit contributed 44 +/- 17% (rats) and 31 +/- 26% (dogs) of the total liver venous vascular resistance under control conditions. We conclude that the portal and sinusoidal vasculatures are the dominant, but not exclusive, resistance sites of the liver venous vasculature both at rest and during norepinephrine-induced vasoconstriction.

Animals↗

PubMed1991

Mechanical characteristics and active tension generation in rat intestinal arterioles.

The contributions of active and passive wall tension to regulation of arteriolar diameters were determined for large (1A), intermediate (2A), and small (3A) arterioles in the small intestine of the anesthetized rat. Active tension (Ta) contributed greater than 85% of total wall force at rest in 2A and 3A and 75-80% of total force in 1A. Ta was approximately 90% of peak active tension (Ta,peak) for large through small arterioles, even though absolute Ta varied by fourfold. A linear relationship between microvascular pressure and Ta was observed for decreases in pressure in all arterioles. Ta remained nearly constant for pressure increases of 40% in 2A and 3A but was increased in 1A. Because of the plateau of the circumference-Ta relationship near Ta,peak, superfusion of progressively increasing concentrations of norepinephrine or adenosine resulted in maintenance of the close Ta-Ta,peak relationship unless the vessel diameter changed greater than 25%. These results indicate that, while arteriolar diameters vary substantially, near-peak Ta is generated for a variety of physiological conditions.

Adenosine↗

PubMed1991

Structural and functional origins of suppressed acetylcholine vasodilation in diabetic rat intestinal arterioles.

This study evaluated the possible impairments to endothelium-mediated vasodilation by structural and functional properties of the intestinal arterioles in adult (20-21-week-old) rats after 8-11 days or 7-8 weeks of streptozotocin-induced diabetes. Arteriolar intravascular pressures and luminal diameters were simultaneously measured during iontophoretic application of acetylcholine, bradykinin, and nitroprusside to the outer vessel wall, and passive diameter-pressure relations were obtained during maximal vasodilation. Microvascular pressures and circumference-passive wall tension relations were similar between all diabetic and normal rats and did not appear to significantly influence vasodilation. Both acute and chronic hyperglycemia were associated with near complete suppression of acetylcholine-induced vasodilation in large arterioles, and the threshold dose for vasodilation of intermediate arterioles was approximately 10-fold higher in diabetic rats. In both diabetic groups, dilatory responses to nitroprusside were normal, and in chronically diabetic rats, the relative vasodilation in response to various doses of bradykinin was equivalent to that found in normal rats. These observations indicate that a very specific deficit of acetylcholine-induced endothelium-derived relaxing factor action rapidly develops in intestinal arterioles of diabetic rats, but the arteriolar wall mechanical properties, cGMP-mediated muscle relaxation, and endothelial release of the bradykinin-stimulated relaxing factor are not compromised after 7-8 weeks of chronic hyperglycemia.

Acetylcholine↗

PubMed1990

Maturation of the rat intestinal microvasculature from juvenile to early adult life.

The same region of intestinal ileum was compared in the same rats at 10 and 20 wk of age to determine if reported differences in vessel density between these ages were the result of changes in vessel numbers. The number and branching pattern of arterioles observed remained remarkably constant during the 10 wk between observations, and minimal enlargement of bowel mass occurred. No significant change in average maximum diameter of arterioles was observed. Although the total number of small arterioles did not change, vessels were gained and lost at an equal rate (7%) between 10 and 20 wk. There was no significant changes in means or frequency distributions of intercapillary distances in the radial or longitudinal bowel muscle layers. The results indicate that the intestinal microvascular branching pattern changes very little from juvenile to adult life. However, a slow turnover of small arterioles does occur, indicating an ongoing remodeling of the terminal vasculature during juvenile life.

Aging↗