Raised intracellular sodium does not cause myogenic contraction of resting rat 150-microns mesenteric resistance vessels.
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Animals↗
Biomedical subjects
C Aalkjaer
Publications and source records attributed to C Aalkjaer.
Sodium metabolism in rat resistance vessels.
Using 22Na we have investigated the Na metabolism in rat mesenteric resistance vessels (internal diameter about 200 micron). The intracellular Na content was determined by washing the vessels at 0 degrees C in saline with Li substituted for Na, and was related to smooth muscle volume determined from measurements of media thickness and internal diameter using light microscopy. On this basis an internal Na concentration of 13.7 mmol l-1 cells was found. The efflux of Na into saline at 37 degrees C consists of two phases, a fast one and a slow one, where the slow phase was considered to be intracellular. It had a rate constant of 0.137 min-1, which was decreased by 50% if 1 mM-ouabain was added to or K withdrawn from the efflux medium. The gain of cell Na after addition of 1 mM-ouabain was much faster than would be expected from the decrease in efflux, indicating that 1 mM-ouabain increases the permeability to Na.
Animals↗
Functional and morphological properties of human omental resistance vessels.
We have examined the functional and morphological properties of arterial resistance vessels with lumen diameters about 200 micrometer from the human omentum. The vascular smooth muscle cells were circumferentially oriented and arranged in about 3 layers within the media. The cells, when held at a length where their contractile response was maximal, were 97 micrometer long and had a mean diameter of 3.9 micrometer. In response to maximum potassium stimulation the force developed per cell was 2.4 micro N. The maximum response to norepinephrine (NE) was about 90% of the response to potassium, while the sensitivity to NE (NE-ED 50 = 0.4 micro M) was about the same as the NE sensitivity reported for larger human vessels. The sensitivity to NE was unaffected by cocaine, while the response to potassium was unaffected by phentolamine. Fluorescence microscopy indicated that the vessels contained few adrenergic nerve terminals. These findings suggest that although the vessels are well supplied with alpha-receptor, the vessels are only of minor importance for sympathetic blood pressure control.
Adrenergic Fibers↗
Effect of age on noradrenaline sensitivity of mesenteric resistance vessels in spontaneously hypertensive and Wistar-Kyoto rats.
1. We have compared the noradrenaline sensitivity of 150 micron arterial resistance vessels taken from a specific place in the mesenteric bed of spontaneously hypertensive (SH) rats and of control Wistar-Kyoto (WK) rats at three ages: 6 weeks, 12 weeks and 24 weeks. 2. The noradrenaline sensitivity of the vessels under normal conditions was the same at all ages in both SH and WK rats (ED50 about 3 mu mol/l). 3. After addition of cocaine (which inhibits the uptake of noradrenaline in the nerve terminals) all vessels became more sensitive to noradrenaline, but at all ages the increase in sensitivity was greater in the vessels of SH rats, suggesting that the smooth muscle cells in these vessels had a greater intrinsic noradrenaline sensitivity than the vessels of WK rats. 4. Since elevation of the blood pressure in the SH rats occurs mainly between the ages of 6 and 12 weeks, the results suggest that the greater intrinsic smooth muscle cell sensitivity of the SH rat vessels is a factor which is amongst the primary factors responsible for the development of hypertension in the SH rat.
Aging↗
Morphological and mechanical properties of small mesenteric arteries and veins in spontaneously hypertensive rats.
Segments of small mesenteric arteries(approximately 150 micrometer lumen diameter) and of corresponding veins were taken from 5-month-old spontaneously hypertensive rats(SHR) AND FROM AGE MATCHED Wistar Kyoto (WKY) controls. The segments were mounted on a myograph which enabled their mechanical and morphological parameters to be investigated simultaneously. Compared with the WKY arteries the lumen diameter of the SHR arteries was smaller while the media thickness and active wall tension response were greater. On the other hand there were no differences between the corresponding veins from SHR and WKY animals although, compared with the arteries, the veins had a greater lumen diameter, a smaller media thickness and a smaller tension response. The findings suggest that the morphological and mechanical differences seen in arteries from SHR are not found on the venous side.
Animals↗
Direct evidence that the greater contractility of resistance vessels in spontaneously hypertensive rats is associated with a narrowed lumen, a thickened media, and an increased number of smooth muscle cell layers.
The mechanical and morphological properties of segments of certain precisely defined resistance vessels (approximately 150 micrometer lumen diameter) in the mesenteric bed of spontaneously hypertensive (SHR) and normotensive (WKY) rats have been compared in vitro under carefully controlled conditions and also after fixation. At a given transmural pressure, the relaxed SHR vessels (compared with the WKY vessels) would have had a 16% smaller lumen diameter (P less than 0.01) and a 49% thicker media (P less than 0.005), so that the media volume per unit segment length was 31% greater (P less than 0.05). The smooth muscle cells were arranged circumferentially in about four layers in the SHR vessels and in about three layers in the WKY vessels. The SHR active wall tension in response to potassium was 53% greater (P less than 0.02) and to norepinephrine was 50% greater (P less than 0.01) than for WKY. However, the ED50 values for the norepinephrine dose-response curves were similar (approximately 5 micrometer). Activation with potassium plus norepinephrine gave greater responses in both vessel types, than with either agent alone, but the SHR responses were on average only 19% greater than the WKY (P less than 0.10). However, under these conditions, the SHR vessels would have been able to contract against 45% greater transmural pressures (P less than 0.001) because of their smaller lumen. On maximal activation, the mean force developed by each cell (approximately 3.85 micro N) was the same in both vessel types, even though on average (P = 0.10) the SHR cells had a 21% greater cross-sectional area. The results support the Folkow hypothesis that in genetic hypertension the increased peripheral resistance is associated with structural changes in the resistance vessels.
Animals↗
Short chain fatty acids relax isolated resistance arteries from the human ileum by a mechanism dependent on anion-exchange.
Ileal resistance arteries (internal diameter 184-337 microns) were discussed out under microscope and mounted in a microvascular myograph for isometric tension recording. Experiments were designed to test compounds trophic to the small intestine, namely, epidermal growth factor, glutamine and the three short chain fatty acids, acetic, propionic and butyric acid, for effects on vascular tone. Glutamine in concentrations up to 30 mM and epidermal growth factor in concentrations up to 1 microM had no contractile or relaxant effects on the resistance arteries. The three short chain fatty acids alone and in combination, however, caused a concentration-dependent (range 0.1-30 mM) relaxation of resistance arteries precontracted with 50 mM KCl. This relaxant effect was significantly inhibited by the presence of the anion-exchange inhibitor 4,4'-diisothiocyanatostilbene-2,2'-disulphonic acid whereas it was unaffected by removal of the endothelium, presence of indomethacin, propranolol or phentolamine. These data suggest that the trophic effects of glutamine and epidermal growth factor on the small intestinal mucosa cannot be explained through actions on the resistance vasculature. In contrast, the relaxant effect of short chain fatty acid on resistance arteries in vitro suggests that these compounds may be able to improve the microcirculation in vivo. An improved microcirculation will, all things considered, facilitate the growth of the small intestinal mucosa.
4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗
Effects of ATP and UTP on [Ca2+]i, membrane potential and force in isolated rat small arteries.
We have investigated excitation-contraction coupling mechanisms associated with the activation of purinoceptors and putative pyrimidinoceptors by assessing the effects of ATP and UTP on cytoplasmic Ca2+ activity ([Ca2+]i), membrane potential (Em) and force in rat mesenteric small arteries. UTP induced a sustained concentration-dependent contractions, closely associated with concentration-dependent increases in [Ca2+]i. Superfusion with 0.1 mM UTP caused a sustained depolarisation of 12 +/- 1 mV (SE, n = 8). In Ca(2+)-free medium, the increase in [Ca2+]i and the contraction obtained with UTP (1 mM) were both transient and were inhibited by prior exposure to noradrenaline (NA). In vessels depolarised with KCl, UTP caused no change in Em, but a sustained increase in force and a transient increase in [Ca2+]i were induced, leading to an increased force/[Ca2+]i ratio. Similar effects on [Ca2+]i, Em and force were observed with ATP; but the effect of ATP on force was transient, whereas the effect on [Ca2+]i and Em declined only slowly. There was no crosstachyphylaxis between the responses to ATP and UTP: in the presence of 1 mM of either, the other drug induced contractions in low concentrations, as if they acted through distinct receptors. The results suggest that both UTP and probably ATP release intracellular Ca2+, possibly from the stores emptied by NA. The sustained response to UTP appears to be due to an influx of extracellular Ca2+. UTP but not ATP was found to enhance the force-generating effect of [Ca2+]i.
Adenosine Triphosphate↗
Effects of pH on vascular tension: which are the important mechanisms?
The pH has marked effects on the blood flow in several vascular beds but the underlying mechanisms remain incompletely understood. It is still not agreed, for example, whether it is the fall in extracellular pH or intracellular pH that is responsible for changes in tone resulting from hypercapnic acidosis. The issue has been further complicated by the recent discovery that nitric oxide (NO) may also be involved in vasodilator responses to hypercapnia with the result that, in some laboratories, attention has been focused away from vascular smooth muscle. The recent availability of fluorescent dyes sensitive to pH has enabled some of the uncertainties in this field to be addressed. In light of these new observations, we have attempted to put older viewpoints in perspective. We conclude that, whilst a fall in smooth muscle intracellular pH is likely to be responsible for immediate responses to acidosis, the extracellular pH probably plays the predominant role in the steady state. The role of NO is best investigated in the cerebral circulation where it plays an important modulating role in the response to acidosis, and is probably of extravascular origin.
Acidosis↗
Myocardial ischemia and ventricular arrhythmias in relation to left ventricular mass and resistance artery structure.
The study comprised 83 patients, mean (+/-SD) age 47 +/- 8 years, with essential hypertension. Systolic and diastolic blood pressure at inclusion were 171 +/- 16 and 110 +/- 7 mm Hg, respectively. Two small resistance arteries were dissected from a subcutaneous gluteal biopsy and mounted in an isometric small vessel myograph for measurement of the media:lumen ratio. Left ventricular mass (LVM) was estimated by echocardiography, and the occurrence of ventricular arrhythmias was assessed by ambulatory ECG for 48 h. Left ventricular hypertrophy (LVH) occurred in 67% of the patients. Systolic function was generally unimpaired. ST depression was found in 75%, and ventricular arrhythmias in 45%. Twenty-two patients had permanent ST depression, and they had also greater LVM and more frequent ventricular arrhythmias than those without permanent ST depression. The area under the ST trend curve of all significant ST depressions was correlated to the LVM (r = 0.42, p < 0.001). Patients with arrhythmias had significantly greater area under the ST trend curve of all significant ST depressions than patients without arrhythmias (p < 0.05). In patients with LVH and permanent ST depression, the media:lumen ratio of the peripheral vessels was greater than that of patients with LVH but without permanent ST depression (11.6 +/- 2.9 vs. 9.8 +/- 2.0, p < 0.01). This suggests that hypertensive structural changes similar to those observed in peripheral vessels might occur in the walls of myocardial resistance arteries.
Adult↗
Changes in noradrenaline sensitivity and morphology of arterial resistance vessels during development of high blood pressure in spontaneously hypertensive rats.
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Aging↗
Ouabain binding and Na+ content in resistance vessels and skeletal muscles of spontaneously hypertensive rats and K+-depleted rats.
The possible role of Na+ in the development of hypertension in rats was explored in measurements of intracellular Na+, 22Na efflux, and 3H-ouabain binding sites in resistance vessels and skeletal muscles. In resistance vessels obtained from 13-week-old spontaneously hypertensive rats (SHR) or age-matched Wistar-Kyoto rats (WKY), (Na)i, total or ouabain-resistant 22Na efflux, and the concentration of 3H-ouabain binding sites showed no significant differences. Soleus muscles obtained from 6-week-old and 13-week-old SHR contained 5 to 11% more 3H-ouabain binding sites than those of WKY. The small difference in ouabain binding probably was related more to variations in growth rate and strain than to the hypertension. In SHR and WKY the Na+ and K+ contents of gastrocnemius muscles were almost identical at 6 and 13 weeks of age. By contrast, in Wistar rats in which the (Na)i of skeletal muscle was increased sixfold by K+ depletion, the systolic blood pressure was decreased by 10%. The K+ depletion was associated with a 35 to 55% decrease in the concentration of 3H-ouabain binding sites in both resistance vessels and skeletal muscles. The results provide no support for any simple cause-effect relationships between either elevated (Na)i or altered concentration of 3H-ouabain binding sites and hypertension in SHR.
Animals↗