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Biomedical subjects

D F Bohr

Publications and source records attributed to D F Bohr.

At least 91 records · Page 5Linked to original sources
PubMed1981

Relaxation of vascular smooth muscle by isoproterenol, dibutyryl-cyclic AMP and theophylline.

There is evidence that the relaxation of vascular smooth muscle produced by isoproterenol or cyclic AMP is mediated by membrane hyperpolarization. The current study investigates the possibility that this hyperpolarization, and hence the relaxation, may be produced by activation of the electrogenic sodium pump. Rat and pig tail artery strips were placed in a 1.0-mM potassium solution for 15 min. This procedure results in a decrease in the activity of the sodium pump. The strips were then made to contract in response to norepinephrine. Two minutes later, the concentration of potassium was increased to 6.0 mM and a relaxation occurred. The amplitude of this relaxation reflects the activity of the sodium pump. Either isoproterenol or dibutyryl-cyclic AMP causes an enhancement (time or degree) of potassium-induced relaxation. Theophylline potentiated potassium-induced relaxation in pig arteries but not in rat arteries. The relaxant action of isoproterenol on 1.0 mM barium contractures of rat arteries was inhibited by treatment with ouabain or with potassium-free solution. Ouabain inhibited the relaxant action of isoproterenol in pig arteries contracted with depolarizing potassium solution but not in rat tail arteries. Dibutyryl-cyclic AMP, theophylline and nitroprusside caused relaxation of serotonin-induced contractions; however, in rat arteries these responses were not inhibited by ouabain or by the absence of potassium. Similar studies on tail arteries from baboons, dogs, pigs and cats showed that relaxation by dibutyryl-cyclic AMP or by theophylline had some dependency on the activity of the sodium pump. These observations are consistent with the following conclusions: 1) isoproterenol and cyclic AMP potentiate the electrogenic pumping of sodium and potassium responsible for potassium-induced relaxation; 2) the relaxing action of isoproterenol, dibutyryl-cyclic AMP and theophylline are dependent upon experimental conditions and the species from which the vascular tissue is obtained; and 3) there is a component of isoproterenol- and cyclic AMP-induced relaxation which is not altered by inhibition of the electrogenic sodium pump in the rat.

Animals↗
PubMed1981

Calcium antagonism is no rose.

Much remains to be defined about the mechanism of action of calcium entry blockers. The diversity of their pharmacological actions reflects the many effects of the calcium ions which they block. The observation that D-600 decreases myogenic tone in the rabbit basilar artery, whereas it increases this tone in the facial vein, is cited as an example of this diversity.

Animals↗
PubMed1981

Cimetidine prophylaxis for gastric ulcers in laboratory swine.

Bleeding gastric ulcers were a major cause of morbidity and mortality in young swine subjected to surgery, chronic catheterization, and daily experimental manipulation. Some of the animals died suddenly due to exsanguination into the gastrointestinal tract, while others survived for several days following the onset of clinical signs. These signs included dark, tarry stools, lethargy, pale mucous membranes, decreased appetite, and dyspnea. Abnormal clinical laboratory findings included decreased hematocrit, hemoglobin and erythrocyte counts indicative of chronic blood loss anemia. On postmortem examination, single or multiple ulcers of variable sizes were found in the nonglandular cardiac portion of the stomach, and the gastrointestinal tract often contained blood. Histologically, the ulcers had a base of granulation tissue with surface suppuration. Prophylactic treatment of these ulcers was initiated using cimetidine, a histamine II blocker. The drug was administered via the drinking water at 15 mg/kg body weight/day. Fourteen of 62 (22.5%) pigs that did not receive cimetidine developed bleeding ulcers. Of 45 animals given daily prophylactic doses of cimetidine, none manifested clinical signs indicative of a bleeding ulcer. These results indicated that cimetidine was effective in preventing morbidity and mortality due to bleeding gastric ulcers in young swine used in chronic laboratory experiments.

Animals↗
PubMed1980

Vascular reactivity in hypertension: altered effect of ouabain.

Ouabain inhibits the relaxing effect of Ca2+ (but not of Mn2+) on contractile responses in tail artery strips isolated from spontaneously hypertensive and normotensive rats. The magnitude of ouabain inhibition was greater in vascular strips from hypertensive rats suggesting a significant difference in basic membrane function in hypertensive vascular smooth muscle.

Animals↗
PubMed1980

Inactivation of released norepinephrine in rat tail artery by neuronal uptake.

The relationship between adrenergic nerve activity and neuronal uptake was investigated. Helically cut strips of rat tail artery were mounted in organ chambers and isometric contractions were recorded. Spontaneous contractions were occasionally observed and these contractions were blocked by phentolamine. Cumulative addition of cocaine produced contractions of the strips. These contractions were blocked by phentolamine and reduced after denervation with 6-hydroxydopamine. Cocaine potentiated the contractile responses to exogenous norepinephrine and caused a shift to the left in the concentration--response curve. Contractions in response to low-frequency field stimulation were potentiated by cocaine; contractions produced by high frequencies were not altered by the drug. Cocaine had no effect on contractions produced by depolarization of the prejunctional membrane with high potassium. The relative rates of relaxation following high- and low-frequency stimulation were increased similarly by cocaine. The results indicate (1) the spontaneous activity of rat tail artery is related to the leakage of norepinephrine from nerve endings; (2) contraction in response to cocaine alone probably results from inhibition of neuronal uptake and the release of endogenous norepinephrine; and (3) the amine uptake mechanism is not operative during depolarization of prejunctional membrane.

Animals↗
PubMed1980

Prostaglandins and potassium relaxation in vascular smooth muscle of the rat. The role of Na-K ATPase.

We explored the hypothesis that postaglandin-induced vasodilation is caused by activation of the electrogenic sodium-potassium pump which results in membrane hyperpolarization and relaxation of vascular smooth muscle. Helical strips of rat tail artery relax in response to potassium after norepinephrine-induced contractions in physiological salt solution containing a low-potassium concentration. The amplitude of this potassium relaxation is used as an index of sodium-potassium ATPase activity. It was observed that PGA1, PGE2, and PGF2alpha (10(-6) g/ml) significantly enhanced the magnitut. PGE2 caused relaxation of contractions induced by either 25 mM KCl or norepinephrine (10(-9) g/ml), and these relaxations were inhibited by 10(-4) M ouabain. Indomethacin (5.3 x 10(-6) g/ml) and meclofenamate (10(-6) g/ml) reduced the magnitude of potassium-induced relaxation by more than 30% of control. PGF2alpha (10(-5) g/ml) reversed the inhibition of potassium relaxation by meclofenamate. These observations suggest that prostaglandins induce vascular smooth muscle relaxation by stimulation of the sodium pump and that endogenous prostaglandins normally potassium relaxation.

Animals↗
PubMed1979

In vitro effects of desoxycorticosterone on vascular smooth muscle.

We present evidence in accord with the observations of S. Kalsner (Br. J. Pharmacol. 36: 582-593, 1969) that in the rabbit aorta, desoxycorticosterone (DOC) potentiates the contractile response to certain catecholamines by inhibiting their degradation by catechol-O-methyltransferase. In contrast, DOC depresses the contractile responses in rat aorta and tail arteries. To elucidate the mechanism of this depression the effect of DOC was evaluated under various conditions. DOC depressed the contractile response to epinephrine, phenylephrine, KCl, and angiotensin II. The depression was unaltered by ouabain or by a potassium-free solution, indicating that DOC did not produce its depression by altering Na-K-ATPase activity. The depression is unaltered in a chloride-free solution, demonstrating that the DOC effect is not caused by a change in membrane permeability to chloride. Radioisotope studies demonstrate that DOC does not alter membrane permeability to potassium. Removal of extracellular calcium with EGTA (ethylene glycol-bis (beta-aminoethyl ether) N, N'-tetraacetic acid) significantly reduced the magnitude of the DOC depression. Indirect evidence is presented suggesting that DOC might increase calcium binding to the plasma membrane, resulting in its stabilization and hence in a depression of the contractile response.

Angiotensin II↗
PubMed1979

Potassium relaxation of vascular smooth muscle from spontaneously hypertensive rats.

Helical strips of tail artery from spontaneously hypertensive (SHR) and Kyoto Wistar normotensive rats (WKY) were observed to relax in response to potassium after contraction induced by norepinephrine in potassium-free solution. Helical strips from SHR consistently showed greater relaxation in response to the addition of potassium than did those from WKY. The amplitude of potassium-induced relaxation is believed to be an index of the activity of electrogenic sodium-potassium transport and hence of sodium-potassium ATPase. Thus, the sodium-potassium ATPase activity of SHR vascular smooth muscle is increased as compared to WKY. This interpretation is supported by the observation that ouabain eliminated potassium-induced relaxation in both SHR and WKY strips. Potassium-induced relaxation in SHR was more sensitive to ouabain inhibition than in WKY. Relaxation induced by potassium in SHR and WKY strips was also shown to vary with: (1) the length of incubation in potassium-free solution, and (2) the concentration of potassium added back. The results of these experiments on potassium-induced relaxation serve as evidence that SHR have either an increased intrinsic sodium-potassium ATPase activity, or an enzyme activity that has been stimulated to a greater degree by an elevated intracellular sodium concentration which resulted from the incubation in potassium-free solution.

Animals↗
PubMed1978

Mechanism of membrane stabilization by calcium in vascular smooth muscle.

In this study we observed relaxation in helical strips of rat tail artery in response to high concentrations of calcium after contraction induced by 10(-7) g/ml norepinephrine. This action of calcium on vascular smooth muscle contraction is referred to as the "membrane-stabilizing effect" of calcium. The current study demonstrates that changes caused by many of the variables that alter this relaxation induced by calcium parallel changes in relaxation in response to potassium; both are attenuated by ouabain, low sodium, reduced temperature, and low potassium. Relaxation produced by manganese is not similarly affected. Because potassium has been shown to cause relaxation of vascular smooth muscle by increasing the activity of sodium-potassium ATPase, we conclude that the relaxation produced by high concentrations of calcium is dependent on the activity of sodium-potassium ATPase; that produced by manganese is not.

Animals↗
PubMed1978

Potassium-induced relaxation as an indicator of Na+-K+ ATPase activity in vascular smooth muscle.

Helical strips of rat tail artery were observed to relax in response to potassium after contraction induced by 10(-7) g/ml norepinephrine in potassium-free solution. After several minutes of relaxation, the strips showed an abrupt redevelopment of tension. The amplitude of the potassium-induced relaxation was employed as an index of the activity of the electrogenic sodium-potassium pump and hence of the Na+-K+ ATPase. This assumption seemed justified because the observed amplitude of potassium-induced relaxation paralleled known effects of the following variables on Na+-K+ ATPase: (1) intracellular sodium concentration; (2) ouabain administration; (3) magnesium; (4) temperature, and (5) potassium concentration. The relaxation that occurred in response to potassium is suggested to be due to an enhanced Na+-K+ ATPase resulting in increased electrogenic transport of sodium and potassium and, consequently, hyperpolarization. We propose that potassium-induced relaxation of rat tail artery may be used as a functional indicator of Na+-K+ ATPase activity in vascular smooth muscle.

Adenosine Triphosphatases↗
PubMed1978

Whole body vascular reactivity during the development of deoxycorticosterone acetate hypertension in the pig.

A change in vascular reactivity was characterized in the pig during the development of deoxycorticosterone acetate (DOCA) hypertension. Pigs, 8-12 weeks of age, were subjected to unilateral nephrectomy and instrumented with an electromagnetic flowprobe on the ascending aorta and with Tygon catheters in the aorta and thoracic vena cava. Approximately 2 weeks after surgery, Silastic strips impregnated with DOCA (100 mg/kg) were implanted subcutaneously. Within the first 3 days after implantation, mean arterial pressure (MAP) began to rise and reached levels approximately 40% greater than control during the 4th week. Graded intravenous infusions of norepinephrine or angiotensin II were given to unanesthetized pigs before, and at intervals during, the development of hypertension. Changes in total peripheral resistance were calculated from recordings of MAP and cardiac output. Comparison of pre-DOCA response curves with those obtained at intervals following DOCA implantation demonstrated a significant increase in vascular smooth muscle sensitivity (decrease in threshold infusion rates) to both drugs post-DOCA. There also was a shift to the left in the dose-response curves. These changes in systemic vascular reactivity occurred at the time the arterial pressure began to rise. The temporal relationship suggests that the increase in vascular reactivity may initiate the increase in mean arterial pressure.

Angiotensin II↗
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↗
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↗