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Biomedical subjects

K Hermsmeyer

Publications and source records attributed to K Hermsmeyer.

At least 91 records · Page 5Linked to original sources
PubMed1977

Mechanism of potassium relaxation of arterial muscle.

Strips of arterial muscle were prepared from rat tail and femoral arteries and dog mesenteric arteries. All muscles developed a contracture slowly when exposed to a potassium-free solution, but relaxed rapidly when potassium was added to the bath to give a concentration as low as 0.1 mM. The slow contracture is caused by norepinephrine release from intrinsic nerve endings, but the rapid relaxation occurs while the norepinephrine concentration is still high. Contractions produced by exogenous norepinephrine or serotonin in a potassium-free bath were also made to relax by the addition of potassium. After several minutes these relaxations reversed abruptly and spontaneously to return to their original level of contraction. The rapid relaxation was found to be due to an electrogenic transport mechanism which caused hyperpolarization within several seconds after the addition of potassium. This hyperpolarization is believed to be caused by electrogenic ion transport since it exceeded the expected membrane potential based on the potential calculated from potassium concentrations, EK. Hyperpolarization declined within 5-15 min, allowing contraction to redevelop. Ouabain was found to prevent both the potassium-induced relaxation and the cessation of norepinephrine release. However, ouabain prevented relaxation as effectively in denervated as in innervated smooth muscle. We conclude that the initial relaxation of arterial smooth muscle that occurs when potassium is reintroduced into a potassium-free solution is caused by membrane hyperpolarization resulting from the enhanced activity of an electrogenic pump; it is not caused by cessation of norepinephrine release.

Animals↗
PubMed1977

Trophic influence of the sympathetic nervous system on the rat portal vein.

Adrenergic denervation of the rat portal vein was produced in vivo by the sympatholytic agent 6-hydroxydopamine (6-OHDA). Treatment of rats with 6-OHDA decreased the responses of the portal veins to nerve stimulation, reduced 3H-norepinephrine (NE) uptake, and decreased catecholamine fluorescence, indicating that partial adrenergic denervation was achieved. The main findings of this study indicate that the in vivo denervation produced: (1) a (time-dependent) increase in sensitivity of the veins to NE, which was not of prejunctional origin, (2) an increase in sensitivity to BaC12, and (3) a partial depolarization of the myovascular cells. The results suggest that the in vivo denervation of the portal veins by 6-OHDA produces a postjunctional alteration, which may be due to the removal of a trophic influence of the sympathetic nervous system. It is proposed that the partial depolarization and associated ionic changes may be components of the mechanism. These results provide the first direct evidence that membrane excitability changes are involved in trophic nerve-muscle interactions in blood vessels.

Animals↗
PubMed1977

Specificity of altered electrogenesis of membrane potential in hypertension.

Cardiac and hepatic portal venous muscle were used in an attempt to determine the specificity of the altered membrane potential (Em) electrogenesis found in caudal artery of spontaneously hypertensive rats (SHR). Neither the sensitivity to norepinephrine nor the electrogenesis of Em was found to be different in SHR than in their normotensive controls. Thus, ventricular myocardium and portal venous myovascular cells do not show either the increased sensitivity or the Em factor proposed as a contributor to it. A second determination of specificity was stimulation of the caudal artery by Ba2+. Both depolarization and extent of contraction were no different in SHR than in normotensive controls, suggesting that the increased sensitivity of arterial muscle does not extend to all depolarizing agents. These data define the electrogenesis of Em in cardiac and portal venous muscle of SHR and their controls and provide a test of the hypothesis that altered Em electrogenesis contributes to increased arterial norepinephrine sensitivity seen in hypertension. The data support rather than refute the hypothesis, i.e., the Em alteration was specific for both the muscle showing increased sensitivity and the agent used for depolarization.

Animals↗
PubMed1976

Spontaneous contractions of dispersed vascular muscle in cell culture.

Dispersed vascular muscle cells from chick omphalomesenteric vessels maintained in primary cell culture contracted spontaneously. Six methods which produced contracting isolated muscle cells are described and compared. The combination of dispersion method and culture conditions to produce contracting muscle cells was more critical for vascular than for heart muscle. These findings of continuing pacemaker function demonstrate that functional integrity of isolated vascular muscle cells is possible to maintain. Further indication of the full functional state of the isolated vascular muscle cells was demonstrated by the sensitivity to norepinephrine at a physiological concentration (0.1 muM). Spontaneous contraction frequencies were similar to the range found in situ, and spontanious or norepinephrine-induced contractions had time courses corresponding to intact vessel contractions. This is the first report that isolated vascular muscle cells in primary cell culture retain functional characteristics found in situ and are suitable for pharmacological characterization of individual muscle cells.

Animals↗
PubMed1976

Effects of chlorobutanol and bradykinin on myocardial excitation.

The negative inotropic effect of a commonly used formulation of bradykinin (Sandoz BRS-640) was found to be due to chlorobutanol, a constituent of the preparation. Solutions containing up to 100 mug of crystalline bradykinin/ml had no effect on tension or action-potential shape. Chlorobutanol (500 mug/ml) caused a 30% decrease in contraction amplitude and a 20% increase in action-potential duration. Chlorobutanol lowered conduction velocity and induced conduction failure and automaticity within isolated ventricular muscle strips. Chlorobutanol affected neither positive nor negative treppe. We conclude that bradykinin has no direct action on toad, frog, or rat myocardium. However, chlorobutanol does have direct effects on myocardial cells, acting on the cell membrane and decreasing isometric tension produced by the heart.

Acetylcholine↗
PubMed1976

Ba2+ and K+ alteration of K+ conductance in spontaneously active vascular muscle.

The spontaneous spiking of vascular muscle in hepatic portal vein was converted from a burst pattern to single spiking by K+ concentrations greater than 20 mM. A pronounced decrease in contraction amplitude was always associated with the conversion of bursts of spikes to single spikes. The single spikes were accompanied by contractions that were only 1-5% of the magnitude of the contractions associated with spike bursts. Ba2+ (1 mM) increased the number of spikes per burst in myovascular cells at low(less than 10 mM) K+ concentrations. Even though Ba2+ caused depolarization, which itself tended to cause conversion to single spiking, the number of spikes per burst and contraction amplitude were greater in Ba2+ solutions. The slope of the Em-log [K+]o relationship depended on the time allowed for changes in [K+], and a maximum slope of 36 mV/decade and an extrapolated [K+]i of 160 mM were the highest slope and lowest [K+]i values recorded. Ba2+ slightly decreased (to 28 mV/decade) the slope of the curve but did not alter the intercept at [K+] = 160 mM. Ba2+ caused an increase in input resistance (rin) and depolarization independent of CL- concentration, and thus appeared to decrease K+ conductance. K+ concentration increases tended to increase K+ conductance (decrease rin) with depolarization. Spontaneously active vascular muscle thus appears to have a K+ conductance that can be altered and to show different spike patterns and altered conduction, resulting in a marked change in contractions. The spike pattern appears to depend at least partially on the combination of K+ conductance and Em.

Animals↗
PubMed1976

Electrogenesis of increased norepinephrine sensitivity of arterial vascular muscle in hypertension.

The possibility that the vascular muscle cell might contribute to the development of essential hypertension by being more responsive to norepinephrine because of an inherently lower membrane potential (Em) was investigated. Experiments were designed to test the hypothesis that Em of arterial vascular muscle cells from spontaneously hypertensive rats (SHR) are less negative than those from matched Kyoto normotensive rats (KNR). The caudal artery, a muscular, densely innervated regulating artery 300-400 mum in outside diameter, which is activated by graded (nonspiking) depolarization to produce a maintained contraction, was studied. Vascular muscle cells from SHR always had less negative Em than those from KNR at 16 degrees C, but not at 36 degrees C, over a range of K+ concentrations from 2.7 mM to 150 mM. From the relationship between Em and K+ concentration, intracellular K+ concentration ([K+]i) was estimated to be 150 mM for SHR and 170 mM for KNR. The caudal artery undergoes a large depolarization when K+ is removed from the superfusing solution and a transient hyperpolarization that exceeds the calculated EK (potassium equilibrium potential) when K+ is replaced. The magnitude of the hyper-polarization on returning to 30 mM or 50 mM K+ always was greater for vascular muscle of SHR than KNR. The apparently lower [K+]i and more active (compensating) electrogenic ion transport in the SHR vascular muscle cells thus result in an unaltered Em at body temperature in the physiological range of K+ concentrations. However, depolarization by norepinephrine was greater over the middle of the dose-response curve, and this greater depolarization caused the contractions of SHR arteries to be greater. The altered electrogenesis of the SHR vascular muscle cells is postulated to provide a mechanism for the increased reactivity of arteries to norepinephrein in hypertension.

Animals↗
PubMed1976

Cellular basis for increased sensitivity of vascular smooth muscle in spontaneously hypertensive rats.

There is evidence that hypersensitivity of vascular muscle to neurotransmitters contributes to the development of hypertension. Comparison of the caudal arteries of spontaneously hypertensive rats (SHR) and their genetically related Kyoto-Wistar normotensive control rats (KNR) showed that although there is no difference in membrane potential under unstimulated conditions, greater depolarization of the SHR vascular muscle cells by norepinephrine occurs at concentrations which cause greater contraction. The mechanism for the increased depolarization and resulting increase in contraction appears to be a lower intracellular potassium ion activity in SHR vascular muscle cells, which results in a lower contribution of potassium gradient to membrane potential. Experiments to determine the sensitivity of isolated, dispersed chick omphalomesenteric vascular muscle cells to neurotransmitters showed remarkably low thresholds to the neutransmitters norepinephrine, serotonin, and acetylcholine, but not potassium chloride. The high sensitivity of isolated cells to neurotransmitters suggests that factors in the intact vessel may cause thresholds to be high, possibly implying that alterations in a neurotrophic mechanism might be responsible for changes in vascular muscle sensitivity in situ.

Acetylcholine↗
PubMed1976

In vitro denervation of the portal vein and caudal artery of the rat.

The effects of 6-hydroxydopamine (6-OHDA) on the isolated portal vein and caudal artery of the rat were studied to investigate the possibility of producing in vitro adrenergic denervation of these blood vessels. Loss of nerve function was determined by field stimulation of the nerves, using short pulses, and by 3H-norepinephrine (NE) uptake. Addition of 6-OHDA produced contractions of both veins and arteries. Two hours after treatment with 6-OHDA, the contractile responses of the caudal arteries and portal veins to field stimulation were reduced to undetectable levels. At this point, the vessels were unable to take up 3H-NE and incubation of the preparations with l-NE failed to restore the contractile responses to nerve stimulation. Prejunctional supersensitivity to l-NE was observed in the portal vein after 6-OHDA but hot in helically cut strips of caudal artery. Prejunctional supersensitivity of the caudal artery to NE was seen, however, if the vessel geometry was kept intact, suggesting that the uptake mechanism for catecholamines only plays a major role in the termination of action of exgenous NE when norepinephrine is applied through the nerve plexus. We conclude that in vitro treatment with 6-OHDA rapidly produces functional adrenergic denervation of both portal vein and caudal artery of the rat and provides an accurate assessment of the importance of the neuronal uptake mechanism to NE sensitivity.

Animals↗
PubMed1976

Adrenergic neuronal degeneration induced in portal vein and caudal artery by 6-hydroxydopamine in vitro.

Fluorescence histochemistry and electron microscopy were used to study the structural consequences of in vitro exposure to the sympatholytic agent 6-hydroxydopamine on two blood vessels, the portal mesenteric vein and caudal artery of the rat. The results showed depletion of catecholamines to indetectable levels associated with clear signs of adrenergic nerve degeneration, such as cytoplasmic shrinking, virtual absence of dense core vesicles and swelling of mitochondria. All of the changes observed occurred within 2 hours in the caudal arteries and 3.5 hours in the portal veins. Comparison of electron and fluorescence micrographs of incubated control specimens with those of unincubated, fresh specimens showed that the nerve endings of the incubated controls were well preserved for at least 3.5 hours. With destruction of nerve endings in such a short period of time, the processes of specific neuronal degeneration could be clearly demonstrated in isolated blood vessels.

Animals↗
PubMed1972

Loss of the plateau of the cardiac action potential in hypertonic solutions.

The effect of hypertonicity on the electrical properties of vertebrate myocardial cells was studied in ventricular muscle fibers of guinea pig, cat, frog, and chicken. The latter two species do not have a T-tubule system, whereas the former two do. In hypertonic solutions (2 x isotonic) produced by addition of sucrose or excess of NaCl, cell diameter decreased and there was a slight hyperpolarization and decrease in action potential overshoot. In guinea pig and cat, the hypertonic solution caused a decrease in input resistance and the plateau of the action potential to disappear in some of the cells; contractions of the entire ventricle also became depressed. These effects were reversed by returning the muscle fibers to isotonic solution. Addition of 5 mM SrCl(2) to the hypertonic solution also caused the plateau component and contraction to reappear. In frog and chick cells, loss of the plateau component and contraction never occurred in hypertonic solution, and input resistance increased. Urea and glycerol hyperosmolarity (2 x) caused no loss of the plateau component or contraction. If the frog and chicken ventricular, and guinea pig atrial myocardial cells (all of which lack T tubules) were to serve as an adequate control for possible effects of hypertonicity on the surface membrane and on contractile proteins, then the results suggest that swelling of the T tubules of mammalian myocardial cells leads to loss of the plateau component.

Action Potentials↗
PubMedDate not supplied

Measurement of whole-cell calcium current in voltage-clamped vascular muscle cells.

The direct measurement of transmembrane calcium current in single vascular muscle cells has been accomplished recently using the whole-cell voltage-clamp technique. The small size of the vascular muscle cell and the proportionately smaller magnitude of its inward calcium current necessitate refined instrumentation, but also make the vascular muscle cell an ideal candidate for whole-cell voltage-clamp recording. Calcium current in vascular muscle cells appears to have some, but not all, characteristics in common with calcium currents similarly isolated in neuronal and cardiac cells, including voltage-dependent activation and steady-state inactivation of calcium current, the presence of two current types, and sensitivity to inorganic and organic calcium channel modulating drugs. Future voltage-clamp analysis of calcium currents in vascular muscle is needed to further our understanding of the control of the calcium channels in physiological and pathophysiological states.

Animals↗