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Biomedical subjects

K Hermsmeyer

Publications and source records attributed to K Hermsmeyer.

At least 73 records · Page 4Linked to original sources
PubMed1983

Effect of hydralazine on tension and membrane potential in the rat caudal artery.

To determine whether the vasodilator, hydralazine (HYD), produces hyperpolarization of vascular muscle cells, we measured the effect of HYD on membrane potential and contractile responses to phenylephrine and K+. HYD (1 microM) caused a 4 mV hyperpolarization of phenylephrine-depolarized arteries (compared with controls without HYD), which could possibly account for up to three-fourths of the 39% decrease in tension measured. K+-contracted vessels were also 34% relaxed by 1 microM HYD without an effect on membrane potential. In addition, HYD further relaxed phenylephrine-stimulated vessels previously relaxed by D-600, suggesting that Ca++ channel blockade may not be an important mechanism of vasodilation for HYD. The evidence suggests that a nonmembrane action of HYD on arterial muscle probably multiplies the relaxant effect of membrane potential hyperpolarization. Both mechanisms would attenuate the effects of adrenergic stimulation.

Animals↗
PubMed1982

Norepinephrine sensitivity and desensitization of cultured single vascular muscle cells.

Isolated single vascular muscle cells were used for studies of the inherent norepinephrine sensitivity and the conditions important for detecting highest norepinephrine sensitivity. Rat vascular muscle cell contractions were quantitated from spontaneous contractions during pulse applications of the drugs, with a time course designed to simulate norepinephrine release in situ. Isolated vascular muscle cells showed a sensitivity to norepinephrine two orders of magnitude greater than those found from isolated intact blood vessels. Associated with the high sensitivity, there was a marked reduction in the response to a second application of norepinephrine or phenylephrine. The reduced second response appears to result from desensitization that is more pronounced in cells that have been exposed to only trace concentrations of catecholamines. These data appear to suggest that there might be continuous suppression of transmitter sensitivity that occurs as a result of transmitter exposure, and possibly cell-to-cell associations. Desensitization would at first severely limit the response to norepinephrine by reducing or eliminating the response to prolonged exposure or a second dose. Thereafter, a lessening of the desensitization process on continuous exposure to catecholamines would be the result, in part, of lowered sensitivity and, in part, of a smaller desensitization response. This process would continuously modulate norepinephrine sensitivity, based on the frequency and extent of stimulation, and we have called it the theory of physiological desensitization.

Animals↗
PubMed1982

Rat cardiac muscle single cell automaticity responses to alpha- and beta-adrenergic agonists and antagonists.

Isolated cardiac muscle cells from neonatal rat ventricular myocardium have both alpha- and beta-adrenergic, positive chronotropic responses, with sensitivity to applied adrenergic agents more than 100 times greater than the intact neonatal heart. These highly sensitive isolated single cells and small groups of cells also reveal partial agonist activity of the alpha-adrenergic antagonist, phentolamine, and the beta-adrenergic antagonist, propranolol. The most likely explanation for the high sensitivity is the lack of a desensitization process that could involve both a desensitization substance and changes in receptors. These experiments suggest that all adrenergic antagonists could possibly show partial agonist activity.

Adrenergic alpha-Agonists↗
PubMed1981

Unaltered membrane properties of arterial muscle in Dahl strain genetic hypertension.

To characterize membrane properties of arterial muscle from Dahl strain hypertensive rats, we measured caudal artery contractile sensitivity to norepinephrine and serotonin, membrane potential at 16 and 37 degrees C, and intracellular potassium, sodium, and chloride content. Dahl salt-resistant (R) strain fed low- or high-salt diets and Dahl salt-sensitive (S) strain fed a low-salt diet remained normotensive. The Dahl S strain on high-salt diets became hypertensive after 4 wk of high salt feeding. There was no significant difference in the norepinephrine or serotonin effective concentration (EC) EC50, EC10, or maximum response between the hypertensive and any of the three normotensive groups. Membrane potential measured at 37 and 16 degrees C and electron-probe analysis of intracellular potassium, sodium, and chloride concentration showed no significant differences between the four groups of animals. These results that arterial muscle membrane mechanisms are not altered in genetically hypertensive Dahl salt-sensitive rats.

Animals↗
PubMed1981

Liposome concentration in canine ischemic myocardium and depolarized myocardial cells.

To determine whether liposomes (microscopic phospholipid vesicles) may be useful in delivering drugs to a region of myocardial ischemia, we studied the concentration of positively charged and neutral liposomes containing 131I-albumin and horseradish peroxidase in ischemic myocardium of 20 dogs during the first 4 hours of experimental myocardial infarction. We studied the interaction of liposomes containing fluorescent dyes and horseradish peroxidase with isolated contracting cardiac myocytes. We found that positively charged and neutral liposomes accumulated in poorly perfused myocardium and that positively charged liposomes accumulated in the ischemic region to a greater extent than neutral liposomes [138 +/- 21 vs. 81 +/- 9% (mean +/- SE) of the concentration of liposomes in uninvolved myocardium]. Electron microscopic examination of this myocardium showed liposome contents to be located in the vascular space, in endothelial cells, and in ischemic myocytes. We found high potassium environment and that liposomal contents were scattered throughout the interior of the cells in the electron micrographs of some of the isolated myocytes. Anoxia alone for 20-30 minutes did not modify the liposome-isolated myocyte interaction or cause depolarization of the cells. We conclude that liposomes may be useful as drug carriers to depolarized ischemic myocardium, although significant uptake by normal myocardial cells cannot be expected with lecithin, cholesterol, and octadecylamine liposomes we used.

Animals↗
PubMed1981

Membrane electrical mechanism of basilar artery constriction and pial artery dilation by norepinephrine.

To study the mechanism by which norepinephrine acts on vascular muscle cell membrane, we recorded membrane potential with intracellular microelectrodes in isolated cat basilar and pial arteries. On addition of norepinephrine concentrations less than 1 microM, pial arteries hyperpolarized and relaxed while basilar arteries depolarized and contracted. Relaxation and hyperpolarization of the pial arteries occurred without the need for addition of any other drug, which indicates the relaxation of spontaneous tone. The relaxation and hyperpolarization could be completely blocked by addition of propranolol before exposure to norepinephrine. The depolarization and contraction of both basilar and pial arteries was blocked by the previous exposure to phentolamine. Electrical spikes were not found spontaneously, but could be induced in both arteries by tetraethylammonium and subsequent addition of norepinephrine, blockable by phentolamine. We conclude that membrane property differences between basilar and pial arteries result in qualitatively different effects of norepinephrine.

Animals↗
PubMed1981

Sympathetic cross-innervation of SHR and genetic controls suggests a trophic influence on vascular muscle membranes.

We have attempted to differentiate neural from humoral environmental factors as the cause of altered arterial muscle membrane properties in spontaneously hypertensive rats (SHR). This laboratory has previously reported that alterations in membrane electrical properties appear to be responsible for increased NE sensitivity in caudal arteries from SHR. In this study, caudal arteries were transplanted into innervated or denervated anterior eye chambers of the same (KNR in KNR, SHR in SHR) or the opposite (KNR in SHR, SHR in KNR) strain. Seven weeks later, we measured membrane potential (Em) and norepinephrine (NE) contractile sensitivity (EC50) in both transplanted and host caudal arteries. Caudal arteries from 2-week-old donor animals transplanted into hosts reinnervated and developed Em and NE EC50 values characteristic of the host strain, interconverting between SHR and KNR characteristics in cross-transplantations. In other experiments, the superior cervical ganglion ipsilateral to the transplanted eye chamber was removed 1 day before transplantation to eliminate the influence of sympathetic nerves. Em values were the same in transplants denied sympathetic innervation whether the arteries were transplanted into the same or opposite strains. Although denervation increased NE sensitivity of KNR caudal arteries, sensitivity of arteries from the SHR strain was unchanged. Therefore, without sympathetic reinnervation, there was no interconversion of Em or NE EC50 characteristics between SHR and KNR by cross-transplantation. These results suggest that neural factors control the development of membrane properties of vascular muscle. It appears that the sympathetic nervous system of the SHR has altered trophic influences that contribute importantly to altered membrane properties in hypertension.

Animals↗
PubMed1980

Angiotensin II increases electrical coupling in mammalian ventricular myocardium.

Electrical measurements of current flow in ventricular myocardium immersed in silicone oil showed that angiotensin II increases the cell-to-cell spread of current within seconds. The increases in current spread and conduction velocity occur without any changes in resting membrane potential or maximum rate of rise of the action potential. The concentration range was 10 nM to 10 microM, with an ED50 of 100 nM for angiotensin exposures lasting about 10 seconds. The larges effects were an apparent decrease in resistance through the cellular pathway to 50% of control and a 40% increase in conduction velocity, which returned to control in about 15 minutes. Continuous or repeated exposure to angiotensin caused desensitization to appear. These effects were found with or without denervation by 6-hydroxydopamine and beta-adrenergic blockade by 1 microM propranolol in calf, pig, sheep, and rabbit ventricular myocardium. Therefore, angiotensin appears to increase electrical conduction rapidly and directly in cardiac muscle by decreasing resistance through the cellular pathway.

Action Potentials↗
PubMed1980

Trophic effect of norepinephrine on the rat portal vein in organ culture.

Rat portal veins were maintained in organ culture to study the development of characteristic denervation changes and a possible trophic effect of the neurotransmitter norepinephrine (NE). Vessels maintained in organ culture for 2 days showed supersensitivity to NE and Ba2+, a more rapid rate of relaxation from a Ba2+ contracture, and partial depolarization of the myovascular cells. All of these changes except the quicker relaxation from Ba2+ contracture could be prevented by incubating the preparations in a NE-containing medium. This evidence suggests that functional changes in vascular muscle cells are caused by the removal of a tropic influence of NE, but can be prevented by NE replacement. However, the failure of NE in the culture media to prevent the increased rate of relaxation from Ba2+ contracture found after 2 days in organ culture suggests that NE is not the only trophic influence acting on the portal vein. In addition, incubation of veins in a NE-containing medium produced a marked subsensitivity to the contractile effects of NE, but not BA2+, and thus possible desensitization of noradrenergic receptors. The data thus support a trophic role for NE in the rat portal vein.

Animals↗
PubMed1979

High shortening velocity of isolated single arterial muscle cells.

Surprisingly high shortening velocities (less than 200 msec contraction-relaxation cycles) were found in isolated vascular muscle cells cultured from rat or chick aorta. All of the small fraction cells with such quick contractions had membrane excitation by short duration spikes, rather than the slower graded depolarization of the other cells which produced 20-fold slower contractions.

Animals↗
PubMed1979

Correlation of function and morphology of neonatal rat and embryonic chick cultured cardiac and vascular muscle cells.

To develop morphological criteria which can be applied systematically for the identification of isolated cardiac and vascular muscle cells in mammalian and avian primary cultures, we have correlated structural and staining properties with excitability, contraction, and norepinephrine sensitivity of isolated muscle cells. The primary cultures of cardiac and vascular muscle contained muscle cells and nonmuscle cells. The muscle cells could be clearly identified by action potentials, contractility, and Masson's trichrome stain characteristics, similar to those of cells from intact source heart and blood vessels. Furthermore, the muscle cells were highly responsive to norepinephrine, showing unequivocal increases in contraction frequency. The sensitivity to norepinephrine was found to be very high (ED50 = 2.3 X 10(-9) M) Phase-contrast observation was sufficient to identify muscle cells only when those cells were contracting. There were no unequivocal morphological characteristics that distinguished between quiescent muscle cells and nonmuscle cells in the absence of histochemical staining. Ultrastructural examination by scanning electron microscopy failed to distinguish between muscle and nonmuscle cells. Histological staining was, therefore, the only reliable nonfunctional identification process that separated muscle cells from nonmuscle cells. Primary cultures, containing nonmuscle as well as muscle cells, are an important experimental preparation because the cellular heterogeneity probably minimizes muscle cell loss of function and phenotypic changes. The correlation we have established between cell staining and function will facilitate exploration of single cell properties, which together constitute hearts and blood vessels.

Action Potentials↗
PubMed1977

High sensitivity of cultured cardiac muscle cells to autonomic agents.

We have established conditions under which cultured embryonic myocardial cells are highly sensitive to the autonomic agents norepinephrine and acetylcholine and have determined that the most important factors affecting this sensitivity involve the application protocol. Using cells 3-5 days in culture, isolated from ventricles of 13-day chick embryos, the ED50 for noerpinephrine was 800 pM and that for acetylcholine was 370 pM. These cells were more than 2 orders of magnitude more sensitive than 13-day embryonic hearts freshly isolated, but not dispersed. Intracellular recording of the membrane actions of norepinephrine and acetylcholine on these cultured cells showed changes in pacemaker slope similar to those seen in freshly isolated hearts. These data demonstrate that preparation of ventricular muscle as isolated cells in culture does not necessarily result in the loss of sensitivity to autonomic agents. On the contrary, the isolated cells show the highest sensitivity to norepinephrine and acetylcholine that has been reported for the myocardium.

Acetylcholine↗
PubMed1977

Norepinephrine release in isolated arteries induced by K-free solution.

Helical strips from arteries with a rich sympathetic innervation (rat tail and femoral, and dog mesenteric arteries) develop a sustained contracture when exposed to a K-free physiological salt solution (PSS). The contracture can be blocked by phentolamine and does not occur in arteries whose nerve terminals have been destroyed with 6-hydroxydopamine. The temporal relationship between force development and efflux of NE was determined. Helical strips of rat tail arteries or dog mesenteric arteries were incubated in PSS containing 1-norepinephrine-7-3H([3H]NE). They were then transferred to a superfusion system which allowed isometric recordings and collection of the superfusate for the estimation of [3H]NE content. Following exposure to a K-free PSS force development paralleled NE release and both parameters were potentiated by ouabain. These data demonstrate that this neurogenic mechanism plays a most important role in the K-free contracture of the vascular smooth muscle studied. It is in accord with the observation that NE is released by adrenergic nerves following inhibition of Na+-K+-ATPase.

Animals↗