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Biomedical subjects

R C Webb

Publications and source records attributed to R C Webb.

At least 163 records · Page 9Linked to original sources
PubMed1984

A comparative study of potassium-induced relaxation in vascular smooth muscle of tiger salamanders and rats.

This study compares potassium-induced relaxation in vascular tissue of an amphibian (Ambystoma tigrinum) and a mammal (rat). Aortas (salamanders) and tail arteries (rats) were cut into helical strips for isometric force recording. After norepinephrine-induced contraction in potassium-free solution, arteries relaxed in response to added potassium (1-20 mmol/l). Potassium-induced relaxation was greater in rat tail arteries than in salamander aortas. Half-maximal relaxation occurred at a potassium concentration of approximately 3 mmol/l in both species. Ouabain inhibited potassium-induced relaxation; salamanders were more sensitive to the glycoside than rats. Potassium-induced relaxation decreased as the temperature of the bathing medium was lowered; half-maximal inhibition occurred at 19 and 29 degrees C for salamander aortas and rat tail arteries, respectively. Potassium-induced relaxation also varied with the interval in potassium-free solution, the hydrogen ion concentration (rats only), and the magnitude of norepinephrine-induced contraction. It appears that the cellular mechanism causing potassium-induced relaxation is similar in blood vessels of salamanders and rats. The observations are consistent with the hypothesis that stimulated electrogenic sodium transport produced membrane hyperpolarization and relaxation in vascular smooth muscle.

Animals↗
PubMed1984

Neuraminidase and contractile responses to norepinephrine in rat tail artery.

Sialic acids are negatively charged groups in the carbohydrate side chains of glycolipids and glycoproteins which line the external membrane surface. The goal of this study was to characterize the effect of neuraminidase, which selectively cleaves sialic acids, on contractile activity in vascular smooth muscle. Helically cut strips of rat tail artery were mounted in an organ chamber and isometric contractions were recorded. Following treatment with neuraminidase (0.2 U/ml, 1 h), contractile responses to norepinephrine were significantly greater than control responses. Phasic contractions to norepinephrine in calcium-free medium were not altered by neuraminidase, whereas following calcium depletion with EGTA, contractile responses to added calcium were greater in enzyme-treated strips than in control when activated with norepinephrine. The augmentation of norepinephrine-induced contractions following neuraminidase treatment was reversed by incubation of the arterial strips with N-acetylneuraminic acid (10(-4) M). Neuraminidase had no effect on contractile responses to potassium chloride, angiotensin II, and caffeine. Biochemical assay indicated that approximately 63% of the total sialic acid residues were removed from the arterial strips during incubation with the enzyme. It is concluded that a component for the control of the transmembrane calcium movement in response to norepinephrine is dependent on the presence of sialic acid residues.

Angiotensin II↗
PubMed1984

Comparison of alpha 2 adrenoreceptors on arterial smooth muscle and brain homogenates from spontaneously hypertensive and Wistar-Kyoto normotensive rats.

Alpha 2 adrenoreceptors are located on vascular smooth muscle of the rat tail artery. In the present study this receptor was studied in spontaneously hypertensive (SHR) and Wistar-Kyoto (WKY) rats. Adrenergic agonists were used to produce isometric contractions of helically-cut tail artery strips from SHR and WKY. Clonidine and guanabenz, alpha 2 agonists, were more potent in the SHR than in the WKY (e.g. clonidine: EC50 SHR = 3.5 +/- 0.6 X 10(-8) M; EC50 WKY = 17.0 +/- 0.2 X 10(-8) M; P less than 0.0005). There was no difference in potency between the alpha 1 agonists, phenylephrine and methoxamine. Yohimbine, an alpha 2 antagonist, was more potent in inhibiting the clonidine-induced contraction in the SHR (pA2 = 7.66 versus 7.14). To determine the number of alpha 2 adrenoreceptors, the specific binding of 3H-clonidine to homogenates of tail artery and of five brain areas was also measured. The maximum number of high-affinity sites on the tail artery was threefold greater in SHR than in WKY (31 +/- 5 versus 11 +/- 3 fmol/mg protein, P less than 0.0005). No differences in the number or affinity of alpha 2 receptor sites was found in the hypothalamus, hippocampus, locus coeruleus or parietal cortex of the two strains of rat. There was a difference in the amygdala (SHR: 163 +/- 16 versus WKY: 108 +/- 14, P less than 0.05). The larger number of alpha 2 adrenoreceptors on the vascular smooth muscle in SHR may provide an explanation for the supersensitivity of SHR to adrenergic agonists.

Animals↗
PubMed1983

Relaxation of rat tail artery to electrical stimulation.

Rat tail artery strips relax in response to electrical stimulation (0.1-8Hz, 9V, 1.0msec) following contraction induced by norepinephrine (5.9 X 10(-7)M). The relaxation is not altered by treatment of the strips with atropine, propranolol, tetrodotoxin or indomethacin nor by chemical denervation with 6-hydroxydopamine. Incubation of strips in calcium-free solution reduced the contractile response to norepinephrine and blocked relaxation in response to 4Hz electrical stimulation. Histamine antagonists (H2 receptor subclass: cimetidine, metiamide) inhibited the relaxation to electrical stimulation in a dose-dependent manner. These results suggest that relaxation to electrical stimulation in rat tail artery is modulated by calcium and by the H2 subclass of histamine receptors.

Animals↗
PubMed1983

Ca2+, histamine antagonists and relaxation to electrical impulses in dog coronary artery.

Isolated dog coronary arteries relax in response to electrical stimulation (0.1-8.0 Hz, 9 V, 1.0 ms) following contraction induced by serotonin. Cimetidine, metiamide and ranitidine inhibited this relaxation. The relaxation was not blocked by pyrilamine. Reducing the concentration of Ca+ (0.1 mM) decreased the rate of relaxation whereas relaxation was more rapid when the Ca2+ concentration was increased (3.2 mM). These results suggest that relaxation to electrical stimulation is modulated by Ca2+ and by the H2-subclass of histamine receptors.

Animals↗
PubMed1983

Potassium-induced vascular relaxation in two kidney-one clip, renal hypertensive rats.

This study was designed to characterize potassium-induced relaxation in vascular smooth muscle in two kidney-one clip (2K-1C), renal hypertensive rats. Potassium-induced relaxation was evaluated in the isolated tail artery and in the isolated pump perfused renal vasculature. Both preparations relaxed in response to potassium after contraction induced by norepinephrine in potassium-free solution. Arterial preparations from hypertensive rats showed greater relaxation than did those from normotensive rats. Potassium-induced relaxation in tail arteries from hypertensive rats was more sensitive to ouabain inhibition than those from normotensive rats; the renal vasculature of hypertensive rats did not differ from controls with respect to ouabain sensitivity. Relaxation in response to potassium in isolated tail artery segments varied with the: 1. length of incubation in potassium-free solution; 2. concentration of added potassium; and 3. concentration of norepinephrine added during the potassium-free interval. The amplitude of potassium relaxation is believed to be a functional measure of the electrogenic sodium pump. These experiments support the hypothesis that vascular smooth muscle from 2K-1C renal hypertensive rats has increased electrogenic sodium pump activity, in vitro.

Animals↗
PubMed1983

Alpha-2 adrenoreceptors on arterial smooth muscle: selective labeling by [3H]clonidine.

The specific binding of [3H]clonidine was used to characterize alpha-2 adrenoreceptors on rat tail artery smooth muscle membranes. At 24 degrees C binding of 8 nM [3H]clonidine was rapid T 1/2 of association = 2.1 min) and reversible (T 1/2 of dissociation = 0.7 min). The binding sites for the [3H]clonidine showed the specificity required for the alpha-2 adrenoreceptor. The rank order of potency of inhibitors of [3H]clonidine binding for agonists was clonidine greater than phenylephrine greater than methoxamine and for antagonists was yohimbine and piperoxan much greater than prazosin. Scatchard analysis of the binding data indicated the existence of a single population of binding sites with the maximum number of binding sites, Bmax, equal to 33.5 +/- 0.3 fmoles/mg of protein and the dissociation constant, KD, equal to 7.3 +/- 0.4 nM. There was no evidence for cooperativity (Hill coefficient = 0.96). The inhibition constants, Ki values, of various adrenergic agonists and antagonists for the displacement of [3H]clonidine from tail artery membranes were well correlated with Ki values determined for the displacement of this ligand from rat hippocampal membranes. Similar correlations were found with the potencies of these same agents in producing contractions of isolated tail artery strips. This study confirms the presence of alpha-2 adrenoreceptors on arterial smooth muscle and suggests that these receptors might be important in vascular function.

Adrenergic alpha-Agonists↗
PubMed1982

Vascular reactivity and high dietary eicosapentaenoic acid.

Epidemiologic studies suggest that high dietary intake of eicosapentaenoic acid (EPA), a precursor of the trienoic prostaglandins, is associated with a low incidence and reduced extent of myocardial infarction. Vascular reactivity of isolated aortic strips from rats maintained for 3 weeks on a control diet or on a diet supplemented with menhaden fish oil (17% EPA) was examined with norepinephrine, sodium arachidonate, KC1, PGF2 alpha and nitroprusside. Aortic strips from rats fed the fish oil diet were significantly less responsive to the contractile effects of norepinephrine and arachidonate compared to those from control diet rats. Treatment of aortic strips with indomethacin decreased responsiveness to norepinephrine. The magnitude of the decrease was greater in control rats resulting in a similar vascular response between the 2 groups after blockade. Contractions to arachidonate were abolished by indomethacin. There were no differences in vascular responses to KC1, PGF2 alpha and nitroprusside in aortic strips from control diet rats and those from the fish oil diet rats. Aortic strips from the fish oil diet rats contained more EPA than those from the control diet rats. Thus, the contractile effect of norepinephrine in isolated rat aortic strips is normally augmented by intrinsic prostaglandins, and this augmentation is diminished by dietary intake of EPA.

Animals↗
PubMed1982

Ouabain binding and potassium relaxation in aortas from renal hypertensive rabbits.

This study was designed to characterize the electrogenic sodium pump in vascular smooth muscle from one-kidney one-clip (1K-1C), renal hypertensive rabbits. Two measures of the electrogenic pump were used: 1) [3H]ouabain binding and 2) potassium-induced relaxation. The binding study indicated a significant increase in the affinity of pump sites for ouabain in aortic strips from hypertensive rabbits compared with those from normotensive rabbits (Scatchard analysis). The maximal binding capacity of the binding sites was similar in the two groups of animals, whereas the concentration of ouabain at which half-maximal binding occurred was lower in the aortic strips from hypertensive rabbits. Aortic strips from hypertensive rabbits showed greater sensitivity to the relaxant effect of potassium after incubation in potassium-free solution. The potassium-induced relaxation in aortic strips from hypertensive rabbits was more sensitive to the inhibitory effect of ouabain than that in strips from normotensive rabbits. These results suggest that the increased sensitivity to potassium and ouabain in vascular smooth muscle from hypertensive rabbits is due to an increased affinity of the pump sites for these substances.

Animals↗
PubMed1982

D-600 and the membrane stabilizing effect of calcium in vascular smooth muscle.

Increases in the extracellular concentration of calcium diminish the rate of force development of vascular smooth muscle and cause relaxation of already contracted vascular smooth muscle. These actions of calcium are referred to as the 'membrane stabilizing effect' of the cation. The current study demonstrates that the calcium channel blocker, D-600, antagonizes the membrane stabilizing influence of calcium in isolated strips of rat tail artery. Contraction of the arterial strips was induced by application of methoxamine, KCl or caffeine. During the plateau phase of the methoxamine response, a stepwise increase in the concentration of calcium from 1.6 to 20.1 mM (2 mM increments) elicited dose-dependent decreases in the level of contraction (relaxation). Treatment with D-600 decreased the magnitude of contraction induced by methoxamine and inhibited relaxation in response to calcium. Similar results were observed when KCl was used to contract the arterial strips. The initial rate of force development in response to methoxamine was decreased by elevations in the extracellular concentration of calcium from 1.6 to 20.1 mM. D-600 antagonized this inhibitory effect of elevated calcium on the rate of force development. Contractile responses to caffeine were not altered by changes in the extracellular concentration of calcium nor by the addition of D-600 to the muscle bath. It is concluded that D-600 blocks the transmembrane movement of calcium and interferes with membrane sites which mediate the stabilizing effect of this cation.

Animals↗
PubMed1982

Angiotensin II-induced relaxation of vascular smooth muscle.

The effects of angiotensin II (AII) on contractile tension were studied in vascular smooth muscle from dogs, pigs and rabbits. Helically cut strips of renal veins were mounted in organ chambers and isometric contractions were recorded. Contraction of the venous strips was induced by application of 10(-8) g/ml norepinephrine (NE). Subsequent addition of 5 X 10(-8) g/ml AII caused a triphasic response: (1) there was an initial contraction (subsequent contractions were tachyphylactic in all species); (2) the contraction was followed by a relaxation below the contraction induced by NE (subsequent relaxation responses were tachyphylactic in dog and pig veins), and (3) there was a return from the relaxation to the level of the NE-induced contraction. The duration of the entire response was approximately 5 min. The magnitude of the relaxation varied inversely with the level of the NE contraction when the contractile state was altered by changing the NE concentration. Conditions which inhibit the sodium pump (potassium-free solution and ouabain) and beta-adrenergic blockade with propranolol had no effect on the AII-induced relaxation. The relaxation was temperature sensitive. Inhibitors of prostaglandin synthesis (indomethacin and aspirin) and saralasin attenuated the relaxation in response to AII. Prostaglandins E1 and E2 and arachidonic acid caused relaxation of renal vein strips contracted with NE; the relaxant effect of arachidonic acid was blocked by indomethacin. These results suggest that: (1) All stimulates the synthesis of prostaglandins in isolated venous smooth muscle, and (2) endogenous prostaglandins modulate the response of venous smooth muscle to AII.

Alprostadil↗
PubMed1982

Relaxation to transmural nerve stimulation and exogenously added norepinephrine in porcine cerebral vessels. A study utilizing cerebrovascular intrinsic tone.

The large arteries at the base of the brain in the pig were studied in vitro for their responsiveness to neurogenic and humoral stimuli. Helical strips of these cerebral vessels tonically contracted consistently following application of resting force. The development and maintenance of this tone were not influenced by prior treatment of strips with tetrodotoxin (5 x 10(-7) M), 6-hydroxydopamine (300 micrograms/ml) guanethidine (5 x 10(-6) M), or antagonists of known vasoactive autacoids (i.e., phentolamine, propranolol, atropine). Once tone reached an equilibrated plateau, transmural nerve stimulation and exogenously applied norepinephrine evoked a relaxation. The relative potency of beta-adrenergic agonists in producing a relaxation was isoproterenol greater than norepinephrine greater than epinephrine much greater than terbutaline. The response to norepinephrine, but not that to transmural nerve stimulation, was abolished by beta-adrenoceptor antagonists. The neurogenic response, but not the relaxation to exogenous catecholamines, was blocked by tetrodotoxin and 6-hydroxydopamine and diminished by guanethidine. Vasoactive intestinal polypeptide and adenosine were also potent relaxant agents. These responses, but not the response to transmural nerve stimulation were blocked by alpha-chymotrypsin (1.5 U/ml) and aminophylline (3 x 10(-5) M), respectively. These results suggest that porcine cerebral vessels develop myogenic tone which allows one to examine neural and/or humoral dilator responses without prior spasmogen addition. The vascular beta-receptors appear to be of the beta 1-subtype which is consistent with that found in other species. The nature of the dilator neurotransmitter is unknown, but the functional integrity of the adrenergic nerve terminals appears important for the neurogenic relaxation.

Animals↗
PubMed1982

Vascular smooth muscle in hypertension.

The cause of the elevated arterial pressure in most forms of hypertension is an increase in total peripheral resistance. This brief review is directed toward an assessment of recent investigations contributing information about the factors responsible for this increased vascular resistance. Structural abnormalities in the vasculature that characterize the hypertensive process are 1) changes in the vascular media, 2) rarefication of the resistance vessels, and 3) lesions of the intimal vascular surface. These abnormalities are mainly the result of an adaptive process and are secondary to the increase in wall stress and/or to pathological damage to cellular components in the vessel wall. Functional alterations in the vascular smooth muscle are described as changes in agonist-smooth muscle interaction or plasma membrane permeability. These types of changes appear to play a primary, initiating role in the elevation of vascular resistance of hypertension. These alterations are not the result of an increase in wall stress and they often precede the development of high blood pressure. The functional changes are initiated by abnormal function of neurogenic, humoral, and/or myogenic changes that alter vascular smooth muscle activity.

Angiotensin II↗
PubMed1981

In vivo and in vitro effects of lead on vascular reactivity in rats.

The effects of lead on vascular responsiveness were examined in rats. Adult rats, which had received levels of lead acetate in their drinking water to produce blood levels similar to those seen in some urban human populations, consistently had higher systolic blood pressures compared to age-matched controls. Helical strips of tail arteries from the lead-treated rats displayed a greater force-generating ability in response to the cumulative addition of methoxamine to the muscle bath. There were no differences in ED50 between the two groups. Similar results were obtained when norepinephrine was used. The calcium-entry blocker, D 600, was less effective in reducing in reducing contractions induced by methoxamine in lead-treated rats than in controls. There were no differences between the two groups in responses to KCl or electrical stimulation of nerve endings. Contractile responses to norepinephrine, methoxamine, KCl, and nerve stimulation in arteries from untreated rats were unaltered by addition of lead acetate to the muscle bath. These results demonstrate that hypertension induced by moderate levels of lead intake is associated with an increased vascular responsiveness to alpha-adrenergic agonists.

Animals↗