Biomedical subjects

R C Webb

Publications and source records attributed to R C Webb.

At least 145 records · Page 8Linked to original sources

PubMed1987

Effect of antihypertensive therapy on a vascular change in genetically hypertensive rats.

Isolated tail arteries from stroke-prone spontaneously hypertensive rats (SHRSP), but not normotensive Wistar-Kyoto (WKY) rats, exhibit oscillatory contractions in response to norepinephrine. To establish whether this vascular abnormality is secondary to elevated arterial pressure, SHRSP and WKY were treated with hydralazine and hydrochlorothiazide from weaning to 4 months of age. Hydralazine and hydrochlorothiazide treatment significantly attenuated hypertension development in SHRSP (systolic blood pressure: control SHRSP = 219 +/- 9 mmHg; treated SHRSP = 143 +/- 5 mmHg at 15 weeks of age). Helically-cut tail artery strips from all rats were mounted in tissue baths for isometric force recording and exposed to norepinephrine (6 x 10(-10)-6 x 10(-6) M) for 20 min at each concentration. Oscillatory activity was defined as the sum of the magnitudes of all phasic contractions occurring during the final 10 min of NE incubation. There was no significant difference in the magnitude of oscillatory activity between hydralazine/hydrochlorothiazide-treated SHRSP and control SHRSP. From these results we conclude that norepinephrine-induced oscillatory activity in SHRSP is a primary vascular abnormality that is not secondary to high blood pressure.

Animals↗

PubMed1986

Vasoconstriction: a new activity for platelet-derived growth factor.

Platelet-derived growth factor (PDGF) is a potent mitogen for vascular smooth muscle cells that has been implicated in the pathogenesis of atherosclerosis. The potential role of PDGF in the altered vasoreactivity of atherosclerotic vessels has been studied through an examination of its effects on contractility in the rat aorta. PDGF caused a concentration-dependent contraction of aortic strips and was significantly more potent on a molar basis than the classic vasoconstrictor peptide angiotensin II. Furthermore, PDGF increased the cytosolic free calcium concentration in cultured rat aortic smooth muscle cells. These observations suggest a new biological activity for PDGF that may contribute to the enhanced vasoreactivity of certain atherosclerotic vessels.

Aminoquinolines↗

PubMed1986

Central 6-hydroxydopamine and renal sodium retention in mineralocorticoid-treated rats.

Cerebroventricular administration of 6-hydroxydopamine attenuated the development of deoxycorticosterone hypertension in the rat but did not affect the initial period of renal sodium retention. However, escape from the sodium retention was greater in 6-hydroxydopamine-treated rats. These data support the hypothesis that destruction of central catecholamine-containing neurons influences the renal handling of sodium. The enhanced escape may lead to diminished total body sodium, which attenuates the development of deoxycorticosterone hypertension.

Animals↗

PubMed1986

Contractile responses to ouabain and K+-free solution in aorta from hypertensive rats.

This study characterizes isometric force development in response to ouabain and K+-free solution in isolated aortic strips from spontaneously hypertensive (SHR) and Wistar-Kyoto (WKY) rats. SHR aortas were more sensitive to ouabain than those from WKY (threshold: SHR, 3.1 X 10(-5) M; WKY, 25.6 X 10(-5) M), and force development in response to 10(-3) M ouabain was greater in SHR (SHR, 586 +/- 51 mg; WKY, 245 +/- 24 mg). Monensin, a Na+ ionophore, potentiated contractile responses to ouabain, whereas amiloride, a Na+ channel blocker, and low Na+ solutions depressed contractile responses to ouabain. Contractile responses of SHR aortic strips to K+-free solution were faster than those of WKY aortic strips [time to half-maximal response (t1/2): SHR, 24 +/- 5 min; WKY, 47 +/- 4 min]. Maximal force development by aortic strips from SHR in response to K+-free solution was not different from that of WKY aortic strips (SHR, 808 +/- 34 mg; WKY, 750 +/- 37 mg). Monensin (10(-5) M) increased the rate of force development to K+-free solution to a greater extent in WKY aortic strips than in those from SHR (t1/2: SHR, 3 +/- 1 min; WKY, 4 +/- 2 min). Amiloride and low Na+ solution depressed contractile responses to K+-free solution in both SHR and WKY aortic strips. These observations demonstrate that SHR aortas are more responsive to ouabain and K+-free solution compared with WKY aortas. Contractile responses to ouabain and K+-free solution were sensitive to experimental interventions that alter transmembrane Na+ movements.(ABSTRACT TRUNCATED AT 250 WORDS)

Amiloride↗

PubMed1986

Cold-induced vasodilatation in isolated, perfused rat tail artery.

This study characterizes an in vitro model of the "hunting response" (cold-induced vasoconstriction and vasodilatation). Two-centimeter segments of rat tail arteries (n = 15) were placed in a muscle bath (37 degrees C) and perfused (37 degrees C) at constant pressure (50 mmHg; flow = 14.5 +/- 0.8 ml/min) with physiological salt solution. Arteries constricted (23.7 +/- 2.8% decrease in flow) in response to activation of adrenergic nerves by electrical stimulation (9 V, 0.1-1.0 Hz, 0.1-4 ms). Cooling the bath to 4-12 degrees C (perfusate = 37 degrees C) caused further flow reduction (0-0.5 ml/min) in 14 arteries. After 20-40 min, 12 arteries dilated (7.4 +/- 1.2 ml/min) followed by constriction in 5-10 min. Typically, flow oscillated between periods of prolonged low flow and brief periods of high flow. Phentolamine (10(-6) M in bath) and acute adrenergic denervation blocked flow changes caused by decreased bath temperature. In unstimulated arteries, exogenous norepinephrine (6 X 10(-8) M in bath) decreased flow by 20%. On cooling (7-10 degrees C) flow decreased to zero, but did not oscillate. These results are consistent with the hypothesis that cold-induced vasoconstriction is caused by augmented smooth muscle responsiveness to norepinephrine, whereas cold-induced vasodilatation is caused by a cessation of transmitter release from adrenergic nerve endings.

Animals↗

PubMed1986

Genetic basis for altered vascular responses to ouabain and potassium-free solution in hypertension.

Many properties intrinsic to vascular smooth muscle are altered in hypertension. It is unknown whether these abnormalities are primary traits that may contribute to the etiology of hypertension or whether these vascular differences between the hypertensive and normotensive strains are inherited independently of genetic factors that predispose to hypertension. To determine if genetic factors responsible for the predisposition for hypertension may be the same as or linked to genetic factors determining a specific vascular response, adult stroke-prone spontaneously hypertensive rats (SHRSP), normotensive Wistar-Kyoto (WKY) rats, and progeny of genetic crosses of SHRSP and WKY rats (F1, F2, F1 X WKY, F1 X SHRSP) were studied. Rats were killed and helical aortic strips were mounted in a tissue bath for isometric force recording. Contractile responses to 10(-3) M ouabain (expressed as a percent of force generated to a maximal depolarizing stimulus) were greater in aortas from SHRSP (90 +/- 9%) compared with aortas from WKY rats (38 +/- 5%, P less than 0.05). The half time for contraction in K+-free solution was more rapid in aortas from SHRSP (21 +/- 4 min) when compared with aortas from WKY rats (48 +/- 4 min, P less than 0.05). A significant positive correlation between blood pressure (tail-cuff method) and the contractile response to 10(-3) M ouabain was observed in the segregating F2 progeny. In contrast, no correlation between blood pressure and the half time for contraction in K+-free solution was observed in the segregating F2 progeny.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1986

Genetic association of hypertension and vascular changes in stroke-prone spontaneously hypertensive rats.

Isolated tail arteries from stroke-prone spontaneously hypertensive rats (SHRSP) exhibit oscillatory contractile activity in response to norepinephrine, whereas those from normotensive Wistar-Kyoto rats (WKY) do not. To determine whether the norepinephrine-induced oscillations are related to high blood pressure or to separable genetic differences between strains, the response to norepinephrine was studied in adult SHRSP, WKY, and progeny of genetic crosses of SHRSP and WKY (F1, F2, F1 X SHRSP, F1 X WKY). Helical tail artery strips were mounted in a tissue bath for isometric force recording. Rats were classified as responders if oscillatory activity in the presence of 1.8 X 10(-7) M norepinephrine exceeded 250 mg/10 min (milligrams of force amplitude during a 10-minute interval). The blood pressures (mm Hg +/- SEM; tail cuff method) and percentage of rats exhibiting norepinephrine-induced oscillations were as follows: WKY: 109 +/- 3, 0%; F1: 129 +/- 4, 0%; F2: 150 +/- 4, 38%; F1 X WKY: 137 +/- 3, 9%; F1 X SHRSP: 188 +/- 7, 71%; SHRSP: 207 +/- 7, 100%. The distribution of the frequency of animals with oscillatory activity among the progenies was consistent with the hypothesis that a single gene locus determines the observed difference in oscillatory activity between the WKY and SHRSP strains. The allele from the SHRSP that determines the activity phenotype is recessive to the allele contributed by the normotensive WKY strain. In the segregating F2 progeny, the blood pressure of the responders was higher than that of the nonresponders (161 +/- 6 vs 144 +/- 4 mm Hg; p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Alleles↗

PubMed1986

Calcium and vascular smooth muscle membrane in hypertension.

A major focus of past and recent research in hypertension has been on the characterization of the nature of the vasculature changes which lead to the observed increase in total peripheral resistance responsible for the elevation of arterial pressure. Here we survey recent evidence which suggests that altered handling of calcium is a primary membrane defect in hypertension. Evidence for the primacy of this defect is provided by studies demonstrating a reduced ability of the membrane to bind calcium in diverse tissues from hypertensive animals. The reduced calcium binding ability appears to be responsible for a greater membrane permeability to monovalent and divalent cations. This greater permeability contributes to the increased sensitivity to vasoconstrictor stimuli of vascular smooth muscle in hypertension.

Animals↗

PubMed1985

Functional bases for individualities among vascular smooth muscles.

This review deals with cellular factors that contribute to individualities of vascular smooth-muscle function in different organ systems and at different levels of the vascular tree. Particular attention has been given to: membrane receptors responsive to catecholamines, serotonin, angiotensin II, dopamine, and acetylcholine; membrane properties, including resting and action potentials, and the Na+, K+ ATPase electrogenic pump; regulation of cellular Ca2+; contractile proteins; metabolism, and cell messengers. Differences in membrane receptors appear to be the major basis for the individualities found in various vascular smooth muscles. Differences in cell-membrane properties and Ca2+ regulation are also significant causes of variability. Cell metabolism and contractile proteins contribute relatively less to the individualities of vascular smooth muscle. Too little is known about cell messengers to assess their contribution to this individuality.

Animals↗

PubMed1985

Direct and sensitizing effects of serotonin agonists and antagonists on vascular smooth muscle.

Serotonin has several effects on vascular smooth muscle. In most vascular beds it causes vasoconstriction, but under the proper conditions it can cause vasodilatation. The constrictor response is a result of activation of specific receptors on the vascular smooth muscle, whereas the vasodilator response is mediated in part by the vascular endothelium. In addition to these direct effects on the vascular wall, serotonin can potentiate contractile responses to several other vasoactive agents (norepinephrine, angiotensin II, histamine, etc.). This indirect sensitizing action of the monoamine is probably mediated by activation of the S2 subclass of serotonergic receptors. These complex actions of serotonin on vascular smooth muscle may be altered in disease states such as hypertension.

Animals↗

PubMed1985

Norepinephrine-induced phasic activity in tail arteries from genetically hypertensive rats.

The effects of norepinephrine on contractile force development were studied in tail artery strips from spontaneously hypertensive stroke-prone (SHRSP) and Kyoto-Wistar normotensive rats (WKY). The strips were mounted in physiological salt solution between a fixed base and force transducers; isometric contractions were recorded. Norepinephrine-induced were characterized by fluctuations in contractile activity, whereas contractile responses in arteries from WKY remained constant with time. The magnitude and frequency of phasic responses in SHRSP arteries varied directly with increasing concentrations of norepinephrine (1.8 X 10(-9) to 1.8 X 10(-6) M). The phasic responses induced by norepinephrine in SHRSP arteries were reversed by the following experimental interventions: 1) 10(-4) M ouabain; 2) 20 degrees C; 3) potassium-free solution; 4) 1.0 mM BaCl2; 5) 20 mM KCl; 6) 30 mM tetraethylammonium chloride; 7) chloride-free solution; and 8) 10(-7) M D 600 (calcium channel blocker). It is proposed that the phasic contractile responses to norepinephrine in SHRSP are related to altered movements of calcium and potassium across the cell membrane. This study demonstrates a very distinct functional individuality in the arterial vascular smooth muscle cell membrane of SHRSP.

Animals↗

PubMed1985

Epidermal growth factor, a vascular smooth muscle mitogen, induces rat aortic contraction.

Atherosclerotic arteries have enhanced reactivity to vasoconstrictors, which suggests that features of the atherosclerotic process itself may result in this abnormal responsiveness. Since vascular smooth muscle proliferation is a prominent feature of atherosclerosis, we postulated that vasoactive agonists and smooth muscle mitogens may share certain common cellular mechanisms of action which potentially contribute to this hyperreactivity. To test this hypothesis, we studied the effects of epidermal growth factor (EGF), a well-characterized mitogen, on rat aortic vascular smooth muscle, both in intact aortic strips and in culture. EGF caused contraction (EC50 = 19 nM) of rat aortic strips which maximally was equivalent to 40% of that induced by angiotensin II, a potent vasoconstrictor. EGF increased 45Ca efflux (EC50 = 3 nM) from cultured rat aortic smooth muscle cells, which was an effect shared by angiotensin II and thought to reflect increased cytosolic-free calcium concentration. EGF (7.5 nM) also stimulated growth of these cultured cells to the same extent as 10% calf serum. These results demonstrate that EGF is both a vasoconstrictor and mitogen for rat aortic smooth muscle cells. The similarities in the effects of EGF and angiotensin II suggest that certain common intracellular mechanisms of action may exist for vasoactive agonists and growth factors which may contribute to the altered vasoreactivity of atherosclerotic vessels.

Animals↗

PubMed1985

Vascular responses to sodium arachidonate in experimental hypertension.

This study characterizes vascular responsiveness to sodium arachidonate (C 20:4) in four models of hypertension [deoxycorticosterone acetate (DOCA) hypertensive rats, two kidney-one clip (2K-1C) renal hypertensive rats, spontaneously hypertensive rats (SHR), and psychosocial hypertensive mice]. Isolated arterial strips (aorta, mesenteric artery, tail artery) were equilibrated under optimal resting tension in physiological salt solution for measurement of isometric force generation. Dose-response curves to arachidonate (10(-10) to 10(-4) g/ml) in arteries from DOCA and 2K-1C hypertensive rats were shifted to the left compared to those in arteries from control rats. In arteries from SHR and psychosocial hypertensive mice, the dose-response relationships were unchanged compared to normotensive values. Arteries from DOCA hypertensive and 2K-1C hypertensive rats developed greater maximal contractile responses to arachidonate than controls; maximal responses in arteries from SHR and psychosocial hypertensive mice were unchanged compared to normotensive values. Contractions to arachidonate were inhibited by indomethacin (0.5 and 5 micrograms/ml) and by aspirin (5 and 50 micrograms/ml). The fatty acid, oleate (C 18:1), had no effect on the contractile state of the arteries, whereas prostaglandin F2 alpha caused contraction. These results indicate altered responsiveness to exogenous arachidonate in arteries from DOCA and 2K-1C hypertensive rats, but not in arteries from SHR and psychosocial hypertensive mice.

Animals↗

PubMed1985

Cerebral intraventricular 6-hydroxydopamine prevents vascular changes in the mineralocorticoid hypertensive rat.

The effect of cerebral intraventricular administration of 6-hydroxydopamine (6-OHDA) on blood pressure and vascular smooth muscle responsiveness in deoxycorticosterone acetate (DOCA)-treated rats was assessed. Rats treated with 6-OHDA and DOCA had significantly lower systolic blood pressures (142 +/- 8 mm Hg) than rats treated with DOCA alone (185 +/- 5 mm Hg). After 5 weeks of DOCA treatment, femoral arteries and aortae were excised from these rats, cut helically into strips, and placed in a muscle bath to record isometric force. Dose-response curves to serotonin were shifted to the left in femoral arteries from DOCA-treated rats compared to both control and 6-OHDA-DOCA-treated rats (ED50: DOCA = 6.8 X 10(-8) M, control = 27.9 X 10(-8) M, 6-OHDA-DOCA = 13.4 X 10(-8) M). Arachidonic acid, the prostaglandin precursor, produced greater maximal contractions in femoral artery strips of DOCA-treated rats (358 +/- 56 mg) than in those from controls (115 +/- 31 mg). The maximal response to arachidonic acid in arteries from 6-OHDA-DOCA rats (203 +/- 78 mg) was not different from control values. Ouabain produced a greater maximal response in aortic strips from DOCA rats (658 +/- 165 mg) compared to those from control (196 +/- 72 mg) or 6-OHDA-DOCA (309 +/- 87 mg) rats. We conclude that increased vascular responsiveness to serotonin, arachidonic acid, and ouabain in DOCA hypertensive rats is secondary to a central action of the mineralocorticoid.

Animals↗

PubMed1984

Vascular smooth muscle function and its changes in hypertension.

The contractile state of vascular smooth muscle influences arterial blood pressure and regulates organ blood flow. Current evidence suggests that the contractile apparatus of vascular smooth muscle is composed of thin and thick filaments, and that force generated between these two filaments provides the mechanism for cell shortening. The molecular events that initiate the interaction between these filaments are dependent upon the free sarcoplasmic concentration of activator calcium, which is regulated by the cell membrane and at subcellular sites. Changes in electrical activity of the cell membrane and interaction of pharmacologic agents with membrane receptors alter the cell, causing either a decrease or increase in sarcoplasmic calcium concentration and thus changing the contractile state of the vascular smooth muscle cell. Alterations in the cellular mechanisms that regulate intracellular calcium concentration may contribute to abnormal vascular function in pathologic states. In this brief review, the normal mechanism of vascular smooth muscle contraction is described, and the evidence that indicates that components of the contractile process change in hypertension is examined.

Actins↗

PubMed1984

Diabetes and reactivity of isolated human saphenous vein.

Helical strips of saphenous veins from diabetic (n = 8) and non-diabetic (n = 18) humans were studied in vivo for their responsiveness to several vasoactive agents. Following application of passive force (approximately 20.0 mN), venous strips from non-diabetic humans often developed spontaneous phasic contractile activity (12 out of 18 patients; 2-5 contractions/min). These intrinsic changes in force were seen in venous strips from only one diabetic patient. The phasic contractions were not altered by treatment with phentolamine, whereas the calcium channel blocker, D-600, and calcium-free solution (1.0 mM EGTA) inhibited the phasic contractions. Saphenous veins from diabetic patients developed less maximal, active tension in response to norepinephrine than those from non-diabetic patients. Contractile responses to serotonin, angiotensin II, and elevated potassium concentration in saphenous veins from diabetic patients were not different from those in veins from non-diabetic patients. These observations demonstrate attenuated development of active tension in response to alpha-adrenergic receptor activation and reduced spontaneous contractile activity in venous smooth muscle from diabetic patients.

Aged↗

PubMed1984

Coronary artery reactivity in deoxycorticosterone acetate hypertensive rats.

Helical strips of coronary arteries from normotensive and deoxycorticosterone acetate (DOCA) hypertensive rats were studied in vitro for their responsiveness to a variety of vasoactive agents. After application of passive force (50-400 mg), arteries developed spontaneous tonic contractions. These tonic contractions were not different between the two groups, and the contractions were not altered by inhibitors of neurogenic, prostaglandin, peptidergic, or purine activity. Coronary arteries from DOCA rats were more sensitive (lower effective dose, 50%) to the contractile effects of norepinephrine, serotonin, and potassium chloride relative to those from normotensive rats. Following contraction induced by serotonin, coronary arteries from DOCA rats relaxed less to isoproterenol and adenosine compared with those from control rats. Relaxation of arteries from DOCA rats in response to prostacyclin, nitroprusside, and acetylcholine did not differ from that in coronary arteries from normotensive rats. These observations demonstrate increased vascular sensitivity to constrictor agents and altered relaxation responses to adenosine and isoproterenol in the coronary vasculature of DOCA hypertensive rats.

Acetylcholine↗

PubMed1984

Vascular effects of free radicals generated by electrical stimulation.

Electrical field stimulation (9 V, 1.0 ms, 4 Hz) of isolated segments of rat tail arteries and dog coronary arteries inhibits contractile responses to exogenous norepinephrine and elevated potassium concentration. This inhibitory effect of electrical stimulation is blocked by various agents that alter oxygen metabolism: superoxide dismutase, catalase, glutathione, ascorbate, and dimethyl sulfoxide. The observations suggest that the inhibitory effect is due to an action of oxygen free radical metabolites that are generated by the electrical stimulation of the oxygen-rich buffer. These free radical metabolites have two actions: 1) they oxidize drugs in the experimental system, and 2) they exert a direct inhibitory action on vascular smooth muscle.

Animals↗