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Biomedical subjects

V M Miller

Publications and source records attributed to V M Miller.

At least 127 records · Page 7Linked to original sources
PubMed1990

17 beta-Estradiol augments endothelium-dependent contractions to arachidonic acid in rabbit aorta.

Experiments were designed to determine the effects of chronic estrogen treatment on endothelium-dependent responses to arachidonic acid in the aorta of the rabbit. Ovariectomized rabbits were treated with either placebo or 17 beta-estradiol for 14 days. The aortas were removed, and rings cut from each blood vessel were suspended for measurement of isometric force. In rings contracted with a submaximal concentration of norepinephrine, endothelium-dependent contractions to arachidonic acid were augmented by estrogen treatment. Prostaglandin F2 alpha, E2, the thromboxane analogue U 46619, and prostacyclin contracted aortic smooth muscle. Only the contractions to prostacyclin were augmented by estrogen treatment. Estrogen treatment enhanced the contractions to norepinephrine in aortas with, but not in those without, endothelium; these contractions were not affected by inhibition of uptake of the neurotransmitter. Indomethacin inhibited contractions to norepinephrine in rings with endothelium from estrogen-treated rabbits. These results indicate that chronic treatment with estrogens can affect arterial reactivity to norepinephrine through an endothelium-dependent mechanism that may involve the metabolism of arachidonic acid by cyclooxygenase. The altered sensitivity of the smooth muscle to prostacyclin may contribute in part to the augmented contractions to arachidonic acid with estrogen treatment.

Animals↗
PubMed1990

Electrophysiological analysis of adrenergic neurotransmission and its modulation by chronic denervation in canine saphenous veins.

The present experiments were undertaken to investigate the electrophysiological responses of the canine saphenous vein evoked by perivascular nerve stimulation, norepinephrine or selective alpha adrenergic agonists before and after chronic sympathetic denervation. Unilateral sympathectomy was performed from T12 to L9 in adult female dogs. After 3 to 5 weeks, the denervated saphenous veins were removed. Innervated saphenous veins were obtained from unoperated dogs. In innervated but not in denervated veins, electrical stimulation generated excitatory junction potentials and a slow depolarization. The slow depolarization was inhibited by rauwolscine or phentolamine, but not by prazosin, whereas excitatory junction potentials were not inhibited by alpha adrenergic blockers. Exogenously applied norepinephrine caused a depolarization of the membrane that was inhibited by rauwolscine but not by prazosin. The selective alpha-1 adrenergic agonist, phenylephrine, and the selective alpha-2 adrenergic agonist, UK 14,304, caused depolarization. In denervated veins, the threshold concentrations of norepinephrine or UK 14,304 required to depolarize the smooth muscle cell membrane were reduced. Responses to phenylephrine were not affected by denervation. These results indicate that in the canine saphenous vein norepinephrine, whether added exogenously or released from sympathetic nerves, causes predominant depolarization by activating alpha-2 adrenergic receptors. Denervation augments selectively the electrical response to alpha-2 adrenergic stimulation.

Adrenergic alpha-Agonists↗
PubMed1989

Alpha 2-adrenoceptors and endothelium-derived relaxing factor.

The endothelium can release potent vasodilator substances, in particular prostacyclin and endothelium-derived relaxing factor. The triggers for the release of endothelium-derived relaxing factor include increases in levels of shear stress, neurotransmitters, autacoids, platelet products, and hormones. The endothelium-dependent response to catecholamines involves stimulation of alpha 2-adrenoceptors on the endothelial cells. Indeed, in a number of blood vessels, selective alpha 2-adrenergic agonists cause endothelium-dependent relaxations. These are seen most typically in blood vessels with long-term exposure to high flows and high partial pressures of oxygen. In addition to the release of endothelium-derived relaxing factor, alpha 2-adrenergic agonists can stimulate postjunctional (postsynaptic) alpha 2-adrenoceptors on vascular smooth muscles. These receptors, which are more abundant in hypertensive blood vessels, activate the contractile process. However, the alpha 2-adrenergic vasoconstrictors act as partial agonists (with a limited receptor reserve) and hence their vasoconstrictor response is very sensitive to functional antagonists such as endothelium-derived relaxing factor. Thus, the presence of endothelial cells can blunt the vasoconstrictor response to these substances not only because of an augmented release of endothelium-derived relaxing factor but also because the vasoconstriction that they induce is particularly susceptible to the inhibitory effect of the factor.

Animals↗
PubMed1989

Endothelium-dependent responses and their potential relevance to the distribution of blood flow during hemorrhagic shock.

The endothelium releases vasoactive substances in response to several circulating hormones and to changes in shear stress of the flowing blood across the endothelial surface. Because the distribution of receptors mediating the release of endothelium-derived factors is not uniform along the vascular bed, the vascular endothelium has a potential role in regulating regional blood flow and maintaining peripheral resistance during the course and recovery from hemorrhagic shock.

Animals↗
PubMed1989

Does endothelin-1 mediate endothelium-dependent contractions during anoxia?

Endothelin-1 (ET-1) is a more potent constrictor of femoral venous than femoral arterial smooth muscle. By contrast, endothelium-dependent contractions to anoxia are more prominent in the artery. Unlike those to ET-1, the endothelium-dependent contractions evoked by anoxia are rapid in onset and readily reversible; they are antagonized by Ca2+ entry blockers. ET-1-induced responses are inhibited by endothelium-dependent relaxing factors in canine arteries, and to a lower extent in veins. ET-1 does not augment the production of cyclic GMP in cultured porcine aortic endothelial cells, or in canine arteries and veins, suggesting that the peptide does not evoke the release of endothelium-dependent relaxing factor (EDRF) in canine blood vessels. The endothelium-derived contracting factor (EDCF) released during anoxic contraction cannot be bioassayed, under conditions where ET-1 causes contraction of the bioassay tissue. No ET-1 appears to be released in the extracellular space during anoxic contractions. These findings do not support the hypothesis that ET-1 is the EDCF released by anoxia.

Animals↗
PubMed1989

Differential sensitivity to endothelin in canine arteries and veins.

Experiments were designed to compare the sensitivity of venous and arterial smooth muscle to endothelin and to determine whether contractions to the peptide could be inhibited by endothelium-derived relaxing factor and nitric oxide. Rings of canine left anterior descending coronary, femoral, and mesenteric arteries and femoral and saphenous veins with and without endothelium were suspended for measurement of isometric force. In the presence of indomethacin, phentolamine, and propranolol, endothelin initiated concentration-dependent increases in tension in all rings. The veins were more sensitive to the peptide than were the arteries. Endothelin depolarized the smooth muscle of the saphenous veins and mesenteric arteries; the threshold concentration for depolarization was approximately 100 times lower in the veins (10(-10) M) than in the arteries (10(-8) M). Removal of the endothelium enhanced the sensitivity only of venous smooth muscle to endothelin. However, stimulation of the endothelium in the arteries with either acetylcholine or the calcium ionophore A23187 rapidly inhibited the maximal tension developed to the peptide. Nitric oxide inhibited contractions to endothelin in arteries and veins without endothelium; the inhibition was greater in the arteries than in the veins. These results indicate that venous smooth muscle is more sensitive than arterial smooth muscle to endothelin. In both blood vessels, endothelium-derived relaxing factor(s) can inhibit contractions to the peptide.

Animals↗
PubMed1989

Is nitric oxide the only endothelium-derived relaxing factor in canine femoral veins?

Nitric oxide may be an endothelium-derived relaxing factor in systemic arteries and pulmonary veins. The endothelium-derived relaxing factor of systemic veins has not been characterized. Experiments were designed to determine whether the endothelium-derived relaxing factor of systemic veins shared chemical properties and mechanisms of action with nitric oxide. Rings of the canine femoral vein with and without endothelium were suspended in organ chambers for the measurement of isometric force. In rings without endothelium, relaxations to nitric oxide were augmented by superoxide dismutase plus catalase and were inhibited by hemoglobin, methylene blue, and LY 83583. The endothelium-dependent relaxations to acetylcholine and A23187 were not augmented by superoxide dismutase plus catalase but were inhibited by hemoglobin and only moderately reduced by either methylene blue or LY 83583. Relaxations to sodium nitroprusside were not inhibited by methylene blue and LY 83583. Relaxations to sodium nitroprusside were inhibited by ouabain and K+-free solution; those to nitric oxide were not. These results indicate that although the endothelium-derived relaxing factor released from canine systemic veins shares some chemical properties with nitric oxide, the mechanism by which relaxations are induced by the two differ. A factor dissimilar to nitric oxide but acting like sodium nitroprusside may be released by the endothelium of canine systemic veins.

Acetylcholine↗
PubMed1989

Relaxations to SIN-1, nitric oxide, and sodium nitroprusside in canine arteries and veins.

Experiments were designed to compare the vasodilator properties of SIN-1, the active metabolite of molsidomine, with nitric oxide (NO) and sodium nitroprusside. Rings of canine femoral arteries and veins with and without endothelium were suspended in organ chambers for the measurement of isometric force. SIN-1 and sodium nitroprusside relaxed rings of blood vessels in the presence and in the absence of the endothelium. However, these relaxations were reduced by the endothelial cells in arteries contracted with endothelin and in veins contracted with prostaglandin F2 alpha. In the arteries, SIN-1, sodium nitroprusside, and NO were equipotent in relaxing rings without endothelium contracted with either norepinephrine or prostaglandin F2 alpha; NO was less potent than the other two vasodilators when the arteries were contracted with endothelin. In the veins without endothelium, the potency of the three nitrovasodilators was comparable; the veins were more sensitive to the effects of the dilators when contracted with prostaglandin F2 alpha than with either endothelin or norepinephrine. These results indicate that SIN-1, sodium nitroprusside, and NO are potent dilators of arterial and venous smooth muscle, and that the potency of the dilators can be altered by endothelial cells and the contractile agonist differentially in arteries and veins.

Analysis of Variance↗
PubMed1988

Enhanced release of endothelium-derived factor(s) by chronic increases in blood flow.

Chronic increases in blood flow caused by an arteriovenous fistula augment endothelium-dependent relaxations to acetylcholine. To determine whether endothelial muscarinic receptors are altered, concentration-response curves to acetylcholine were obtained in the presence of pirenzepine in fistula- and sham-operated canine femoral arteries. Pirenzepine inhibited the response to acetylcholine in both arteries. The pA2 (log Kb) for the antagonist was the same. A bioassay system was used to assess release of endothelium-derived relaxing factor. Rings of femoral artery (without endothelium) from unoperated dogs relaxed more when superfused with perfusate derived from endothelium of fistula-operated arteries during acetylcholine stimulation. Rings without endothelium of sham- and fistula-operated arteries relaxed to the same extent when superfused with perfusate derived from the endothelium of unoperated femoral arteries. These results suggest that augmented relaxations to acetylcholine in canine arteries where blood flow is chronically elevated do not result from changes in the subtype of endothelial muscarinic receptors or in the sensitivity of the underlying smooth muscle to endothelium-derived relaxing factor(s). They are likely due to increased release of endothelium-derived relaxing factor(s) on muscarinic activation.

Acetylcholine↗
PubMed1988

Effect of 17 beta-estradiol on endothelium-dependent responses in the rabbit.

Experiments were designed to determine the effect of 17 beta-estradiol on endothelium-dependent responses of isolated arteries. Ovariectomized female New Zealand rabbits were treated either with 17 beta-estradiol (100 micrograms i.m.) or with solvent for 4 days. After excision, femoral arteries were cut into rings and suspended for isometric tension recording in organ chambers filled with modified Krebs-Ringer bicarbonate solution. Rings from the 17 beta-estradiol-treated rabbits showed an enhanced endothelium-dependent relaxation to acetylcholine (3 x 10(-9)-3 x 10(-8) M) in the absence or presence of indomethacin. Under the same experimental conditions, the endothelium-dependent responses to the calcium ionophore A23187 were unchanged. In the absence of indomethacin, the response to adenosine diphosphate was depressed in rings with endothelium taken from animals treated with with 17 beta-estradiol; in the presence of the inhibitor of cyclooxygenase, the endothelium-dependent responses were comparable in blood vessels from treated and untreated rabbits. This study suggests that endothelium-dependent responses of arteries can be modulated by steroid hormones.

Acetylcholine↗
PubMed1987

Endothelium-dependent responses in autogenous femoral veins grafted into the arterial circulation of the dog.

Endothelium-dependent responses differ in arteries and veins of the dog. Experiments were performed to determine whether chronic grafting of veins into the arterial circulation would alter the endothelium-dependent responses of the veins. Segments of femoral veins were grafted to the femoral artery of the dog. 6 wk after surgery the venous grafts were removed from the dog, cut into rings, and suspended in organ chambers for isometric tension recording. In some rings the endothelial cells were removed. Acetylcholine and alpha 2-adrenergic agonists did not cause endothelium-dependent relaxations in venous grafts. The calcium ionophore (A23187) initiated such relaxations which were not mediated by prostanoids. Endothelium-dependent relaxations were also observed in venous grafts to ADP, thrombin, and arachidonic acid. In segments of graft where myo-intimal hyperplasia was prominent, relaxations to ADP, thrombin, and A23187 were blunted and in some segments contractions were observed. These results demonstrate the ability of the endothelium of venous grafts to initiate changes in tone of the smooth muscle.

Acetylcholine↗
PubMed1987

Denervation augments alpha-2 but not alpha-1 adrenergic responses in canine saphenous veins.

Experiments were performed in order to determine the influence of sympathetic denervation on alpha-1 and alpha-2 adrenergic responses in canine saphenous veins. In female dogs anesthetized with sodium pentobarbital, the left lumbar sympathetic chain was excised from L1 to L7. After a 3- to 5-week period, the left (denervated) and right (innervated) saphenous veins were removed, cut into rings and suspended for isometric tension recording in organ chambers filled with modified Krebs-Ringer bicarbonate solution. Denervation reduced significantly the norepinephrine content of the venous rings and the contractile responses evoked by the indirect sympathomimetic amine, tyramine. The contractile responses evoked by exogenous norepinephrine were augmented by denervation under control conditions (16.7-fold shift in concentration-effect curve) and also after inhibition of neuronal and extraneuronal uptake and beta adrenoceptors (3.8-fold shift in curve). Denervation increased the contractile responses evoked by the alpha-2 adrenergic agonist, UK 14,304 (5-fold shift in concentration-effect curve), but not those produced by the alpha-1 adrenergic agonist, phenylephrine. The selective augmentation of alpha-2 adrenergic responses by denervation may reflect the preferential innervation of alpha-2 adrenoceptors in the canine saphenous vein.

Animals↗
PubMed1986

Modulation of endothelium-dependent responses by chronic alterations of blood flow.

To determine whether the blood flow and O2 tension to which a blood vessel is chronically exposed could modulate endothelium-dependent responses, these parameters were altered in the dog either by causing partial occlusion of the femoral artery or by creating a fistula between the femoral artery and vein. Blood flow was reduced by 75% in the clamped artery; mean arterial pressure was unchanged. In the vessels proximal to the fistula, blood flow was elevated and O2 tensions were similar in the vein and artery. After 6 wk the femoral arteries and veins were excised, and their endothelium-dependent responses were studied in vitro. The endothelium-dependent relaxations to acetylcholine, adenosine diphosphate, and alpha 2-adrenergic stimulation were augmented in fistula-operated compared with sham-operated arteries. The responses to these agents in the clamp-operated vessels were not different from those of the sham-operated ones. Relaxation to arachidonic acid in the arteries showed an inverse relationship to blood flow. In the veins proximal to the fistula, the endothelium-dependent relaxations to acetylcholine were augmented and an endothelium-dependent relaxation to alpha 2-adrenergic stimulation was present; only a contractile response was observed in veins from the sham-operated limb in response to the latter. These studies suggest a pattern of increased endothelium-dependent relaxation in vessels exposed to chronically elevated blood flow.

Animals↗
PubMed1986

Vascular smooth muscle responsiveness in a hibernator: effects of season and temperature.

To determine the effects of season, acclimation state, and hibernation on the reactivity of vascular smooth muscle from a hibernant species, strips of thoracic aorta, renal and femoral arteries, and portal vein obtained from adult woodchucks, Marmota monax, were suspended for isometric tension measurements in physiological salt solution. These blood vessels exhibited no seasonal variation in resting tension, connective tissue content, or maximum tension developed to norepinephrine. However, the concentration-response curves to norepinephrine in both aortic and portal vein strips from animals tested in May and June were shifted to the left of those from animals tested in either August or November through February. This increased sensitivity to the catecholamine was seen also in renal vessels from hibernating compared with nonhibernating animals. Decreasing organ bath temperature from 37 to 28 degrees C increased tension developed in response to norepinephrine in aortic and renal strips, whereas that of the femoral artery was unchanged. With further cooling to 17 degrees C, the responses to norepinephrine in aortic and renal strips were similar to the responses at 37 degrees C. The contraction developed to 40 mM KCl was diminished in all tissues at 28 degrees C. Blockade of beta-adrenergic receptors did not augment the response to norepinephrine at 37 degrees C. Contractions of the woodchuck aorta in calcium-free medium were sustained longer than comparable tissue obtained from a rabbit. These data suggest that receptor-mediated processes are modulated in hibernating animals. This modulation varies among vascular beds and may act to maintain or divert perfusion of the tissue through entry, during, and arousal from hibernation.

Acclimatization↗