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J A Bevan

Publications and source records attributed to J A Bevan.

At least 19 recordsLinked to original sources
PubMed1992

Further evidence from an elastic artery that angiotensin II amplifies noradrenaline-induced contraction through activation of protein kinase C.

Angiotensin II (AII, 0.1 nM) increased concentration dependently the sensitivity of rabbit aortic rings to low concentrations of noradrenaline. This was not associated with increases in noradrenaline-induced 45Ca2+ uptake or efflux and was prevented by the protein kinase C (PKC) inhibitors staurosporine (0.01 microM) and calphostin C (0.1 microM). Pretreatment of the rings with PMA (phorbol-12-myristate-13-acetate, 0.1 and 1 microM, 24 h at 4 degrees C) abolished the potentiation phenomenon. We conclude that AII potentiation of noradrenaline-induced vascular tone may be due to a PKC-mediated increase in intracellular sensitivity of the contractile apparatus to Ca2+.

Alkaloids↗
PubMed1992

Vascular alpha-adrenoceptor affinity variation is not due to varying populations of subtypes distinguished by WB 4101 and chlorethylclonidine.

Interaction with chlorethylclonidine has been used to subdivide populations of alpha 1-adrenoceptors in some tissues. WB 4101 can distinguish high and low affinity states of the receptor. The present study was carried out to determine if different populations or affinity states of alpha 1-adrenoceptors distinguished by either of these compounds, could explain the variation in alpha 1-adrenoceptor agonist affinity found amongst rabbit arteries. Five arteries were studied whose affinity for noradrenaline vary between 4.8 and 6.4. These were the thoracic aorta, renal, superior mesenteric, ear and ovarian arteries. WB 4101 was found to be equally effective in antagonizing noradrenaline on all arteries. Chlorethylclonidine caused a 20-fold rightward shift of the noradrenaline dose-contraction curve in the thoracic aorta; but had little or no effect on the other vessels. Thus, the combination of different proportions of subsets of alpha 1-adrenoceptors distinguished by WB 4101 or chlorethylclonidine does not explain the variation in alpha 1-adrenoceptor affinity found in these rabbit arteries.

Adrenergic alpha-Agonists↗
PubMed1992

Comparable sensitivity of flow contraction and relaxation to Na reduction may reflect flow-sensor characteristics.

Physiological salt solution infused through the lumen of a resistance branch of the rabbit central ear artery mounted in an isometric myograph causes both contraction and relaxation. The effect of reductions in extracellular Na up to 26 mM (20% of the NaCl content of the physiological saline solution) on these flow-induced changes in wall force and on the contraction to norepinephrine (10(-6) M) and relaxation to acetylcholine (10(-8) to 3 x 10(-6) M) and papaverine (10(-6) to 3 x 10(-5) M) has been studied. Na in the physiological saline solution was reduced by substitution of NaCl with sucrose or N-methyl-D-glucamine. The effect of either of these substitutions was to reduce both responses, contraction and relaxation, to the same extent. This sensitivity is such that physiological changes in blood Na concentration would be expected to influence flow-induced changes in wall tone. Responses to norepinephrine, acetylcholine, and papaverine were not significantly changed by these alterations in Na. It is argued that since reduction of extracellular Na diminished both contraction and relaxation to a similar extent, leading to relaxation and contraction respectively, that this effect probably occurs at a site common to both flow responses. Because both flow effects occur after endothelium removal and the extracellular matrix binds a large proportion of the Na in the blood vessel wall, this may represent the location of a flow-sensitive mechanism.

Acetylcholine↗
PubMed1992

Magnitude of beta-adrenoceptor-mediated responses of dog epicardial coronary arteries: inverse relation to diameter.

Regional blood flow patterns vary within myocardium to suggest that intrinsic regional differences occur in vasoregulation. Accordingly, we used standard in vitro methodology (isometric force transducer) to study adrenergic responses in epicardial left anterior descending (LAD) artery and right coronary arteries (RCA) obtained from dogs (n = 9). In the presence of propranolol (10(-6) M) and blockers of uptake 1 and 2, norepinephrine (NE) elicited minimal, if any, constriction. After preincubation with phentolamine (10(-6) M) and preconstriction with prostaglandin (PG)F2 alpha or a thromboxane (Tx)A2 analogue, maximum NE relaxation (as % of induced tone) for the RCA was 61 +/- 3 (SE) %, which was significantly greater than the LAD (46 +/- 5%, P < 0.01). ED50 values were not different. Endothelial removal and forskolin relaxations did not change the sensitivity or maximal response between arteries. Expressing beta-adrenoceptor-mediated relaxation as a function of vessel diameter revealed a common regression for RCA and LAD (r = -0.56, P < 0.001). ED50 and diameter were minimally related. Thus the RCA has a greater beta-adrenoceptor response than the LAD in dogs. The difference appears to be reconciled by a common inverse relationship between vessel size and beta-adrenoceptor response. The difference was independent of alpha-adrenoceptor, endothelium, and second messenger processing, suggesting a mechanism based on beta-adrenoceptor density.

Acetylcholine↗
PubMed1992

Neural mechanisms regulating neurohypophysial resistance arteries.

We defined the extent of vasoactive intestinal polypeptide (VIP) and noradrenergic influences on isolated 100- to 200-microns-diameter vessels from the resistance arterial circulation of the neurohypophysis. A dual extracranial (inferior hypophysial) and intracranial (superior hypophysial) arterial supply to the neurohypophysis was confirmed. The inferior hypophysial artery demonstrates noradrenergic and VIP-like perivascular nerves, whereas the superior hypophysial artery shows primarily VIP-like innervation. Pharmacological sensitivity of the inferior hypophysial to VIP [mean effective dose (ED50) = 10(-8.2) M] and to norepinephrine (ED50 = 10(-5.7) M) was demonstrated. The superior hypophysial reacted only to VIP (ED50 = 10(-8.6) M). The physiological relevance of these findings was tested with transmural nerve stimulation. Frequency-dependent vasodilation of both inferior and superior hypophysial arteries was demonstrated. This dilation could not be blocked with atropine or propranolol. Frequency-dependent vasoconstriction was identified in extracranial vessels including the inferior hypophysial artery. This constriction is only partially blocked by prazosin, phentolamine, and guanethidine. When neurohypophysial resistance vessels are compared with larger circle of Willis arteries and similar-size pial vessels of other cerebral regions, they appear to have regionally unique neural mechanisms for regulating blood flow. Specifically whether controlled by periarterial nerves or other tissue influences, the inferior hypophysial artery appears to meet anatomic, pharmacological, and physiological definitions of neural control for both dilator and constrictor activities of flow to the neurohypophysis.

Animals↗
PubMed1992

Electrical field stimulation-mediated relaxation of rabbit middle cerebral artery. Evidence of a cholinergic endothelium-dependent component.

The effects of electrical field stimulation (EFS) of rabbit middle cerebral arteries were examined using wire-mounted arterial segments. EFS of segments maintained at rest tension caused a tetrodotoxin-sensitive sympathetic contraction. In agonist-contracted segments maintained at approximately 60% of tissue maximum force, EFS caused a relaxation in two thirds of the preparations. Maximum response (mean +/- SEM) was 33 +/- 3.5% of maximal relaxation. The EFS relaxation was tetrodotoxin-sensitive but was not blocked by either chronic surgical sympathectomy or exposure to guanethidine (5 microM). Electron microscopy of chromaffin-fixed arterial sections showed the presence of chromaffin-positive large and small vesicles. Within the same sheath of Schwann were also a smaller number of nerve profiles containing many small clear vesicles. Removal of the vascular endothelium or treatment with atropine (10 nM) eliminated the EFS relaxation in approximately 50% of the segments and reduced the response in another 35-40%; in the remainder, relaxation was unaffected. Combined data for endothelium removal and atropine treatment showed that each caused a significant (p less than 0.01) reduction in the EFS relaxation. Atropine also significantly reduced EFS relaxation in guanethidine-treated segments. There was no reduction in EFS relaxation after procedures that antagonized ATP- or substance P-mediated relaxations. These results indicate that EFS of precontracted rabbit middle cerebral artery causes a neurogenic nonadrenergic relaxation. The neuroeffector mechanism mediating this response has a predominantly cholinergic endothelium-dependent component as well as a noncholinergic endothelium-independent component.

Animals↗
PubMed1992

Intraluminal flow increases vascular tone and 45Ca2+ influx in the rabbit facial vein.

The buccal segment of the rabbit facial vein exhibits a high level of myogenic tone in vitro that develops only in stretched vessel segments between 33 degrees and 44 degrees C. The infusion of physiological salt solution into the lumen of 2-mm-long rabbit facial vein segments induced a flow rate-dependent increase in wall tone, both in the presence (37 degrees C) and absence (30 degrees C) of myogenic tone. In calcium-free physiological solution with EGTA, neither flow nor stretch-induced tone was observed. This flow-induced contraction was associated with an increase in 45Ca2+ unidirectional influx and net uptake. These measurements correlated positively with the level of the associated constrictor responses, both in the presence or absence of myogenic tone. The mean contractile responses to flow (10 and 40 microliters/min), stretch, and histamine (1 microM) were 13%, 28%, 24%, and 33% of the tissue maximal response, respectively. When 45Ca2+ influx was expressed in relation to the force development (45Ca2+ influx per milligram), the amount of calcium entry was dependent on the stimulus. Values for 45Ca2+ influx per milligram in response to flow (10 and 40 microliters/min) and to histamine (1 microM) were not significantly different. The value was significantly lower for the response to stretch. On the other hand, 45Ca2+ net uptake, when expressed per unit force, was similar in response to flow (10 and 40 microliters/min), histamine (1 microM), and stretch.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Angiotensin II amplifies arterial contractile response to norepinephrine without increasing Ca++ influx: role of protein kinase C.

We investigated whether the enhanced contractile response to norepinephrine caused by a subthreshold concentration of angiotensin II was associated with an increased 45Ca++ influx or net uptake. Rabbit facial artery segments were mounted isometrically to measure the 45Ca++ influx and net uptake in response to norepinephrine. The contractile response to norepinephrine (3 microM) in the presence of angiotensin II (0.1 nM) was 149.5 +/- 7.4% of control. This response amplification was not associated with changes in norepinephrine-induced 45Ca++ influx or net uptake. Angiotensin II also potentiated the contractile response to caffeine obtained in a Ca(++)-free buffer containing ethylene glycol bis(beta-aminoethyl ether)N,N'-tetraacetic acid (2 mM) to 148.0 +/- 4.8% of control. In both cases, the amplification was prevented by pretreatment with either staurosporine (10 nM) or calphostin C (100 nM), two inhibitors of protein kinase C. We conclude that angiotensin II potentiation of norepinephrine-induced vascular tone occurs in the absence of changes in stimulated Ca++ entry. This potentiation may be due to an increase in intracellular sensitivity to Ca++, possibly mediated by protein kinase C.

Alkaloids↗
PubMed1991

Longitudinal in vivo and in vitro time-course study of chronic cerebrovasospasm in the rabbit basilar artery.

Subarachnoid hemorrhage (SAH) was induced by multiple injections of autologous blood into the prepontine cistern in the rabbit. Long-lasting angiographic narrowing was recorded over a period of nine days after SAH. Papaverine (PPV) reversed angiographic narrowing in the first three days after SAH. Vasospasm was refractory to PPV from day five to day nine after SAH. PPV - refractoriness (in vivo) was positively correlated with decreased vessel wall distensibility (in vitro). Arterial segments showed spontaneous increases in tone in the first two days after SAH. Other alterations observed include a marked gradual reduction in the capacity of the vessel wall to contract, reduction in constrictor nerve influences on vascular tone, and impaired acetylcholine - induced vasorelaxation. Tonic contraction to the maximum dose of serotonin was increased in acute spasm and decreased in chronic spasm. It is suggested that the initial cause of arterial narrowing after SAH is the action of vasoactive substances released in the close vicinity of the arterial wall; this then leads to abnormal tone, tissue damage, and structural changes.

Acetylcholine↗
PubMed1991

Pressure and flow-dependent vascular tone.

Most small arteries are partially constricted in vivo. After excluding neurogenic, metabolic, and circulating as well as local hormonal influences, a sizeable component of tone persists which is commonly called basal tone. In the absence of such tone, cardiac output would be insufficient to maintain the circulation. This review focuses on the contribution of stretch, induced by changes in transmural pressure, and flow acting through shear forces exerted at the blood vessel wall interface, to basal tone. Evidence concerning the cellular processes that may be activated by these physical forces--the mechanotransducing systems--are discussed. The involvement of the endothelium and the role of change in membrane potential are evaluated and lead to the conclusion that pressure and flow effects do not depend exclusively on the release of endothelial factors nor the activation of voltage-gated Ca2+ channels. Stretch/pressure-induced changes in tone show distinctive pharmacological profiles. They are dependent on extracellular calcium and yet in many instances are only weakly affected by organic Ca(2+)-entry inhibitors. Flow-dependent vascular effects, both constrictor and dilator, are both exquisitely sensitive to changes in extracellular Na+ and appear to be related to its transmembrane gradient. Stretch/pressure cause activation of protein kinase C, an intracellular modulator of Ca(2+)-dependent contractile processes. The existence of separate and distinctive cellular sensing and responding systems to pressure and flow raise the possibility that the smooth muscle tone of the vascular system can be influenced independently by the pressure and rate of flow of the blood.

Animals↗
PubMed1991

Variable receptor affinity and tissue sensitivity.

Vascular smooth muscle sensitivity to norepinephrine (NE), measured by contractile responses in vitro, varied in different arteries of the rabbit and also in the same vessels in other species. There was a good correlation between variation in the affinity of NE for the alpha 1-adrenoceptor and tissue sensitivity. The variation was continuous and probably not indicative of different receptor subtypes. Solubilization of alpha 1-adrenoceptors from the membrane changed the affinity for specific ligands while reconstitution restored it. Taken together, these results suggest the presence of a factor(s) within the receptor microenvironment capable of modulating affinity and hence tissue sensitivity to NE. In some blood vessels, receptor number was correlated significantly with affinity of the alpha 1-adrenoceptor for NE also. In general, the contribution of receptor number was considerably less than the affinity for NE.

Animals↗
PubMed1991

Pressure and flow: are these the true vascular neuroeffectors?

Activity of the efferent nerve supply to the vasculature results in local increases or decreases in the tone of the vascular smooth muscle cells with corresponding changes in diameter. This results in changes in pressure and flow, both of which, because they too influence the vascular wall, extend the influence potentially to the entire bed. As the vascular bed is sensitive to pressure - an increase causing vasoconstriction - and to flow - an increase causing variable amounts of contraction and relaxation - the final results must reflect their interaction. Thus, the direct changes in artery tone brought about by neural activity are modified and diffused throughout the entire regional arterial system by the concomitant changes in the flow and pressure of the blood.

Animals↗
PubMed1991

Two indices of functional damage of the artery wall parallel the time course of irreversible narrowing in experimental vasospasm in the rabbit.

Autologous blood placed around the basilar artery caused angiographic narrowing with a biphasic time course. The first immediate phase was reversed by intraarterial papaverine; the second exhibited an increasing component of narrowing which was papaverine-resistant. In vitro studies showed that vessels became increasingly stiffer, less capable to develop active tone, and less responsive to vasoconstrictors and vasodilators. The papaverine-resistant component of angiographic narrowing (in vivo) could be directly correlated with loss of contractility and increased artery wall stiffness (in vitro).

Animals↗
PubMed1991

Augmentation of endothelium-independent flow constriction in pial arteries at high intravascular pressures.

The effects of an increase in intraluminal pressure and flow on the diameter and active smooth muscle tone of pial arteries was studied in perfused segments. Resistance arteries (approximately 250-300 microns i.d.) were perfused under controlled pressure and flow conditions, and changes in arterial diameter registered with an automated video device. In any particular segment, diameter measurements were normalized to that observed at 5 mm Hg. Changes in active wall force were determined by relating the observed diameter under a particular set of conditions to the diameter at the same intramural pressure when smooth muscle tone was inhibited (calcium-free physiological saline solution) and to the diameter when smooth muscle cells were activated close to maximum (KCl; 89 mM). At 60 mm Hg, the diameter decrease of 21% in the absence of flow represented stretch-induced tone. No additional changes in diameter were encountered with a flow of 20 microliters/min. Diameter decreased a further 7% at 100 microliters/min. When intraluminal pressure was 90 mm Hg, diameter decreased 39% without flow. Additional constriction of 10% and 19% occurred at flows of 20 and 100 microliters/min, respectively. At the higher pressure, the vasoconstriction occasioned by flow was significantly greater than that at the lower pressure. After endothelium inactivation by passing hypo-osmotic Krebs' solution followed by air through the segment, mean diameter was less at each combination of pressure and flow, although this difference did not reach statistical significance. The diameter reductions to increases in pressure from 60 to 90 mm Hg and to flow at 40 microliters/min were not altered by endothelium inactivation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Evidence that neuropeptide Y and norepinephrine mediate electrical field-stimulated vasoconstriction of rabbit middle cerebral artery.

We investigated the contractile response of isolated rabbit middle cerebral artery (MCA) segments to electrical field stimulation (EFS). The dynamics of the EFS contraction were compared with a similar-sized branch of rabbit ear artery. In comparison with the ear artery, the EFS contractions of the MCA displayed a longer latency and a higher stimulus frequency threshold. Greater stimulation train lengths were required to attain equilibrium, and the time course of EFS response--including force development, plateau, and return to rest tension--was significantly slower than in the ear artery. Morphological and pharmacological studies of the MCA showed that it receives sympathetic adrenergic innervation: whole-mount preparations displayed catecholamine histofluorescence; electron micrographs of MCA sections revealed a population of varicosities containing chromaffin positive large and small vesicles; and EFS contractions were blocked by tetrodotoxin (30 nM) and guanethidine (5 microM) and by chronic surgical sympathectomy. Exposure to prazosin (10 microM) or phenoxybenzamine (1 microM) blocked norepinephrine contractions but did not significantly influence the EFS contraction. Procedures and drugs that antagonized the responses to neuropeptide Y, serotonin, or histamine were also ineffective in blocking the EFS contraction. The involvement of ATP could not be assessed, since the purinergic P2 agonist alpha,beta-methylene ATP was ineffective in blocking ATP-mediated contractions. The EFS contraction, however, could be blocked by a combination of neuropeptide Y desensitization and phenoxybenzamine (30 nM) or prazosin (0.1 microM). These results suggest that norepinephrine and neuropeptide Y are released from sympathetic nerves and mediate EFS contraction by occupation of postjunctional alpha-adrenoceptor and neuropeptide Y receptors. Since the blockade of only one of these components does not diminish the response to EFS, the adrenergic neuroeffector system in this artery may involve complex prejunctional regulatory mechanisms.

Adrenergic beta-Antagonists↗
PubMed1991

Clentiazem protects against chronic cerebral vasospasm in rabbit basilar artery.

BACKGROUND AND PURPOSE: Experiments were carried out in rabbits to determine whether clentiazem (8-chlorodiltiazem), a cerebrovascular-selective calcium channel blocker, administered 24 hours before subarachnoid hemorrhage influenced the subsequent cerebral vasospasm. METHODS: Subarachnoid hemorrhage was induced by multiple injections of blood into the prepontine cisterns of 35 male New Zealand White rabbits, and clentiazem (5 mg/kg) was administered 4 times daily until sacrifice. Cerebral artery diameter was assessed in vivo by angiography. Functional features of basilar arteries were measured using conventional in vitro methodology. RESULTS: Clentiazem reduced the angiographic narrowing seen on days 2 and 5 from 35% and 34%, respectively (sham control, 1.42 +/- 0.31 mm [n = 22]), to 8% and 11%, respectively, and prevented the narrowing (32%) that occurred on day 9. Narrowing in the untreated rabbits was only partly reversed by papaverine; all narrowing in clentiazem-treated animals was papaverine sensitive. Clentiazem prevented or reduced many of the changes in the basilar artery caused by the subarachnoid hemorrhage. Of particular relevance to arterial narrowing were the increased wall stiffness, the transient spontaneous changes in wall force, and the reduction in relaxation to acetylcholine. Reduction of the changes in wall force induced by agonists and by stimulation of intramural sympathetic nerves was observed. CONCLUSIONS: The vascular damage associated with chronic cerebral vasospasm is related to calcium entry into the smooth muscle and endothelial cells, and possibly sympathetic nerve terminals, through calcium channels sensitive to clentiazem, which suggests that clentiazem may be of value in the management of chronic cerebral vasospasm.

Acetylcholine↗
PubMed1991

Platelets augment rabbit cerebral artery constriction by activating protein kinase C.

BACKGROUND AND PURPOSE: We tested the hypothesis that activated platelets augment cerebral artery responsiveness to thrombin by activating protein kinase C, a possible intracellular modulator of Ca2+ sensitivity. METHODS: Ring segments of rabbit basilar artery were prepared for in vitro measurements of isometric force. Cumulative concentration-response curves to thrombin were made in the absence or presence of activated platelets. RESULTS: Arteries contracted to thrombin in a concentration-dependent manner; freshly obtained human platelets (8.5 x 10(8) cells/ml) activated with 10 micrograms/ml collagen increased the arteries' sensitivity to thrombin by threefold while augmenting the maximal response from 40 +/- 11% to 66 +/- 12% of the maximal response to 0.3 mM histamine. At 10 nM, staurosporine, an inhibitor of protein kinase C activity, blunted the platelet-induced augmentation of the response to thrombin but did not alter the sensitivity or the maximal contraction to 8-64 mM K+. Removal of the endothelium did not alter the characteristics of the thrombin concentration-response curve. The addition of activated platelets increased the tissue sensitivity of endothelium-denuded arteries to thrombin by a factor of 30, and the maximal response to thrombin was 101 +/- 27% of the histamine response. CONCLUSIONS: Our findings suggest that amplification of the arterial contractile response to thrombin caused by platelet-derived mediators may be due to activation of protein kinase C. There may also be a protective role for the cerebrovascular endothelium since endothelium reduced the extent of augmentation of protein kinase C-mediated tone by vasoactive agents released by activated platelets. Thus, increased vascular responsiveness caused by activated platelets may in part be due to protein kinase C-mediated changes in the intracellular sensitivity to Ca2+.

Alkaloids↗