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R C Webb

Publications and source records attributed to R C Webb.

At least 127 records · Page 7Linked to original sources
PubMed1988

Antiserum to angiotensin-binding protein inhibits vascular responses to angiotensin II.

This study characterizes inhibitory properties of an antiserum to an angiotensin-binding protein on vascular responses to angiotensin II. The antiserum was collected from guinea pigs that had been immunized with an angiotensin-binding protein that was isolated from a particulate fraction of rabbit liver. The bioassay system consisted of helically cut strips of rabbit renal artery suspended in organ chambers for measurement of isometric force development. After treatment with the antiserum (1:1,000-1:50 dilution), contractile responses to angiotensin II (10(-8) M) were reduced compared with those measured after treatment with nonimmune serum. At a dilution of 1:50, the magnitude of contractile responses to angiotensin II were approximately 40% of control values. This inhibitory action of the antiserum was similar to that induced by the angiotensin II antagonist, saralasin. Contractile responses to norepinephrine (5.9 x 10(-8) M) were not altered after incubation with the antiserum. These results indicate that the binding protein in hepatic cells may be similar in some respects to the membrane receptor mediating contractions to angiotensin II in rabbit renal arteries.

Angiotensin II↗
PubMed1988

Area postrema ablation and vascular reactivity in deoxycorticosterone-salt-treated rats.

In rats, central administration of the neurotoxin 6-hydroxydopamine prevents hypertension and certain functional vascular changes after deoxycorticosterone (DOC)-salt treatment. In this study, the effect of electrolytic ablation of the area postrema on blood pressure and vascular reactivity in DOC-salt-treated rats was examined. Four treatment groups of rats were studied (n = 5 in each): area postrema lesion, DOC-salt (DOC pivalate, 5 mg/wk s.c. for 5 weeks); sham lesion, DOC-salt; area postrema lesion, control; and sham lesion, control. Helically cut strips of carotid artery, aorta, and mesenteric artery were prepared for isometric force recording. Area postrema lesion attenuated hypertension in DOC-salt rats (mean arterial pressure, 107 vs 123 mm Hg in area postrema lesion and sham lesion rats, respectively; chronic aortic catheter). Vascular strips from sham lesion-control rats. These changes in vascular reactivity also were observed in area postrema lesion-DOC-salt rats. DOC treatment in rats on a normal sodium intake did not result in hypertension or increased vascular reactivity. In summary, integrity of the area postrema is necessary for hypertension but not for changes in vascular reactivity, in DOC-salt rats. It appears that 1) changes in vascular reactivity may be necessary, but they are not sufficient to produce DOC-salt hypertension, and 2) if these vascular changes are secondary to a central nervous system effect, they are mediated by a pathway distinct from the area postrema.

Animals↗
PubMed1988

Adrenal-dependent change in vascular reactivity in stroke-prone spontaneously hypertensive rats.

Tail arteries from stroke-prone spontaneously hypertensive rats (SHRSP) exhibit oscillatory contractions in response to norepinephrine. This type of oscillatory behavior does not occur in tail arteries from normotensive Wistar-Kyoto rats (WKY). We have shown that the traits of norepinephrine-induced oscillatory activity and high blood pressure are genetically associated in SHRSP, suggesting that oscillatory activity is a primary vascular abnormality that contributes to hypertension in this strain. In the present experiments, two approaches were used to test the hypothesis that adrenal mineralocorticoids modulate expression of this genetically determined vascular abnormality in SHRSP. First, the effect of adrenalectomy on blood pressure and oscillatory activity was determined in SHRSP that underwent bilateral adrenalectomy 3 weeks before experimentation. Second, the effect of deoxycorticosterone acetate (DOCA)-salt treatment on blood pressure and oscillatory activity was determined in 1) rats with no genetic background for oscillatory activity (WKY) and 2) progeny of SHRSP x WKY (F1 rats). Helically cut tail artery strips from all rats were mounted in isolated tissue baths for isometric force recording. Vessels were exposed to norepinephrine (6 x 10(-10) to 6 x 10(-6) M) for 20 minutes at each concentration. Oscillatory activity was defined as the sum of the phasic contractile amplitudes for all oscillations occurring during the final 10 minutes of norepinephrine incubation. Adrenalectomy markedly decreased blood pressure and oscillatory activity in SHRSP.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Cortex Hormones↗
PubMed1988

The endothelium partially obscures enhanced microvessel reactivity in DOCA hypertensive rats.

This study examined the contribution of the endothelium to pressor and depressor responses in the isolated, perfused mesentery of mineralocorticoid hypertensive rats. Following uninephrectomy, adult male rats were made hypertensive by subcutaneous implantation of deoxycorticosterone acetate (DOCA; 200 mg/kg); control rats were sham-treated. All rats received drinking water that contained 1.0% NaCl and 0.2% KCl. Following 4 to 6 weeks of treatment, the rats were anesthetized and the mesenteric vasculature was isolated and pump-perfused (constant flow with buffer) to evaluate changes in perfusion pressure. Vascular responses were determined before and after disruption of endothelial function by perfusion with oxygen free radicals generated in the buffer by electrical stimulation. Vasodilator responsiveness to acetylcholine and nitroprusside in the intact mesentery of hypertensive rats did not differ from that in the intact mesentery of normotensive rats, whereas pressor responses to norepinephrine in the intact mesentery of hypertensive rats were greater than normotensive values. Following disruption of endothelial function, depressor responses to acetylcholine were greatly attenuated whereas those to nitroprusside were unaltered or increased. Pressor responses to norepinephrine were potentiated in mesentery that had undergone endothelial disruption, and this potentiation was greater in hypertensive rats than in control rats. The slopes of pressure-flow curves in the presence of norepinephrine were less steep in mesentery with intact endothelium. The flow-modified component of these pressure-flow curves that was related to the endothelium was greater in mesenteric vascular beds of hypertensive rats. These results indicate that a factor released from the endothelium partially masks the enhanced vascular reactivity characteristic of this animal model of mineralocorticoid hypertension.

Acetylcholine↗
PubMed1988

Effects of lead on vascular reactivity.

Considerable controversy exists concerning the possible role of lead in the etiology of human hypertension. In animal studies, there is convincing evidence that lead alters cardiovascular responsiveness; rats drinking water containing 100 ppm lead develop a chronic, significant 15 to 20 mm Hg elevation in systolic blood pressure. Pressor responsiveness to catecholamines is enhanced in animals chronically exposed to lead, and the responsiveness of isolated vascular smooth muscle to adrenergic agonists is increased in rats with lead-induced hypertension. Experimental evidence suggests that alterations in the cellular mechanisms that regulate intracellular calcium concentration may contribute to the abnormal vascular function in lead-induced hypertension. Recent work in our laboratory indicates that increased vascular reactivity in genetic hypertension is associated with altered activity of the protein kinase C branch of the calcium messenger system. Contractile responses to lead in rabbit mesenteric artery are potentiated by activators (phorbol esters) of this enzyme complex, and a selective inhibitor of protein kinase C inhibited contractions induced by lead. Based on these results, it is proposed that a cellular component of the action of lead to increase vascular reactivity may relate to the role of protein kinase C in smooth muscle contraction.

Animals↗
PubMed1988

Parallel effects of DOCA on salt appetite, thirst, and blood pressure in sheep.

Salt appetite was quantified in sheep by measuring the relative amounts of high-salt (266 meq/kg) and low-salt (6 meq/kg) pelleted alfalfa that they ate. Given a choice of these two foods, normal sheep ate twice as much low-salt as high-salt pellets. Following DOCA administration the sheep rapidly developed an increased salt appetite, and after 10 days they ate approximately three times as much high-salt as low-salt pellets. Their choice rapidly reverted to control values after the end of the DOCA treatment. The changes in salt appetite were accompanied by changes in thirst and mean arterial pressure. We hypothesize that these effects of DOCA reflect changes that parallel those this mineralocorticoid causes in the hypothalamic regulatory centers for salt appetite, thirst, and blood pressure.

Animals↗
PubMed1988

Calcium and contractile responses to ouabain and potassium-free solution in aortae from spontaneously hypertensive rats.

This study examines the role of calcium in contractions induced by Na+, K+ ATPase inhibition in blood vessels from spontaneously hypertensive (SHR) and normotensive Wistar-Kyoto rats (WKY). Helical strips of aortae from SHR contract more rapidly in response to ouabain or potassium-free conditions than those from WKY rats. Dose-response curves to calcium in SHR aortae treated with 10(-3) mol/l ouabain were shifted to the left of those in WKY. Treatment with 10(-3) mol/l EGTA shifted dose-response curves to calcium in ouabain-treated strips to the left in both strains. The magnitude of the leftward shift induced by EGTA was greater in WKY aortic strips than in those from SHR. Similarly, treatment with EGTA increased the rate of contractile responses to potassium-free solution in WKY aortae to a greater extent than in SHR aortae. Verapamil (10(-6) mol/l) depressed contractions induced by ouabain and potassium-free solution and abolished the differences between SHR and WKY aortae in terms of contraction rate. Calcium-free conditions completely blocked contractions caused by sodium pump inhibition. These results suggest that the difference in responsiveness to sodium pump inhibition in SHR and WKY rats results from an alteration in calcium entry through verapamil-sensitive calcium channels.

Animals↗
PubMed1987

Cyclosporine augments reactivity of isolated blood vessels.

Administration of cyclosporine (CS) as an immunosuppressive agent in clinical transplantation is associated with multiple side effects including nephrotoxicity and hypertension. These two effects could be related in that the renal changes may be secondary to alterations in organ blood flow. The present studies investigate the ability of CS to augment contractile responsiveness in blood vessels from normotensive rats. Isometric force generation was measured in isolated tail arteries and portal veins. CS (8.3 X 10(-6)M) potentiated tail artery contractile responses to sympathetic nerve stimulation, exogenous norepinephrine, and increases in extracellular potassium concentration. Portal veins undergo spontaneous contractions which are related to the firing of calcium-driven action potentials in the smooth muscle cells. CS significantly increased the frequency of these spontaneous contractile events. These results suggest that components of CS toxicity may involve a direct action on vascular smooth muscle and/or on vascular adrenergic neurotransmission.

Animals↗
PubMed1987

Calcium influx and vascular reactivity in systemic hypertension.

Numerous studies have focused on functional vascular changes that characterize the hypertensive state. Recent evidence that suggests that increased vascular reactivity in hypertension is due to changes in the delivery of activator Ca++ through channels in the cell membrane will be reviewed. The primary evidence supporting this hypothesis comes from studies that characterize the effects of Ca++-free solution and calcium channel blockers on contractile properties of isolated vascular smooth muscle. In the present study, experiments were performed to investigate the role of Ca++ influx in vascular contractions produced by interventions that cause membrane depolarization. Isometric tension development in helical strips of carotid arteries from stroke-prone spontaneously hypertensive rats in response to elevated K+ and tetraethylammonium chloride was greater than that in carotid arteries from Wistar-Kyoto normotensive rats. The rate of tension development to K+-free solution in carotid arteries from stroke-prone spontaneously hypertensive rats was faster than in Wistar-Kyoto normotensive rat arteries. Contractile responses to all 3 depolarizing interventions were reduced in arterial strips incubated in Ca++-free solution containing the chelator ethylene glycol bis-(beta-aminoethyl ether) N,N,N',N'-tetraacetic acid and in arterial strips treated with the Ca++ channel blocker verapamil. These results are consistent with the hypothesis that constrictor stimuli that produce membrane depolarization cause an opening of Ca++ channels in the plasma membrane that are sensitive to the organic channel blockers. Further, a change in Ca++ permeability or membrane depolarizing mechanisms contributes to increased contractile responsiveness in carotid arteries of stroke-prone spontaneously hypertensive rats.

Animals↗
PubMed1987

Effect of cooling on vascular smooth muscle from the thirteen-lined ground squirrel.

Peripheral vascular resistance in the ground squirrel (Spermophilus tridecemlineatus) increases when the animal enters hibernation. The goals of this study were to determine if a change in vascular reactivity contributes to this hemodynamic response, and to compare the effects of temperature on vascular responsiveness in a hibernator (ground squirrel) and a nonhibernating mammal (rat). Helically cut strips of aortae and femoral arteries were mounted in organ chambers (37 degrees C) and isometric contractions were recorded. The arteries were made to contract in response to exogenous norepinephrine (5.9 X 10(-7) M). Cooling the organ chamber (11 degrees C) potentiated contractions to norepinephrine (5-15% increase) in ground squirrel femoral arteries but depressed those (80-100% decrease) in ground squirrel aortae and rat aortae and femoral arteries. Contractions in response to depolarizing concentrations of potassium in ground squirrel femoral arteries were depressed by cooling (11 degrees C), suggesting that the augmented response to norepinephrine at low temperature is specific. Treatment with indomethacin, propanolol, and ouabain did not alter the potentiating effect of temperature on contractions to norepinephrine in ground squirrel femoral arteries. Apparently, the potentiation is not related to prostaglandins generated in the vascular wall, to blockade of beta-adrenergic receptors, nor to inhibition of the electrogenic sodium pump. The observations are consistent with the hypothesis that a change in vascular responsiveness contributes to the regional control of blood flow in hibernation. This adaptive response is specific in that it does not occur in the aorta of the ground squirrel and the response is not present in the vasculature of the rat, a nonhibernating mammal.

Animals↗
PubMed1987

Contractile responses to ouabain and potassium-free solution in vascular tissue from renal hypertensive rats.

This study characterizes contractions to ouabain and potassium-free solution in isolated vascular segments from two-kidney, one clip (2-K, 1C) hypertensive rats. Aorta, mesenteric artery, and vena cava from hypertensive rats were more sensitive (lower threshold) to ouabain than those from normotensive rats. Contractions of hypertensive vascular segments to potassium-free solution and to ouabain (10(-3) mol/l) were faster than those in normotensive vessels. Monensin potentiated contractions to ouabain and increased the rate of force development to potassium-free solution to a greater extent in normotensive aortae than in hypertensive aortae. Amiloride, low sodium solution, verapamil and calcium-free solution depressed contractions to ouabain and potassium-free solution in both hypertensive and normotensive aortae. These observations demonstrate augmented responsiveness to ouabain and potassium-free solution in hypertensive blood vessels. Interventions which influence transmembrane sodium and calcium movements altered contractions to ouabain and potassium-free solution. The results are consistent with the hypothesis that vascular cells of hypertensive rats have enhanced sodium pump activity.

Animals↗
PubMed1987

Free radical-mediated endothelial damage in blood vessels after electrical stimulation.

The endothelium plays an important role in mediating vasodilator effects of several agents (acetylcholine, thrombin, A23187, etc.). The goal of this study was to determine the ability of oxygen free radicals generated by electrical field stimulation to alter endothelial function in isolated tissue systems. Tail artery strips and the mesenteric microvasculature isolated from Sprague-Dawley rats were used. Following smooth muscle contraction induced by norepinephrine, these preparations relaxed in response to acetylcholine chloride or ionophore A23187. All vessels were then subjected to electrical stimulation (9 V, 1-2 ms, 4 Hz) of the physiological buffer in which they were bathed or perfused. In some of these preparations, an antioxidant, (10(-4) M sodium ascorbate, 3.6 X 10(-5) M glutathione, 1.3 X 10(-2) M dimethyl sulfoxide) was included in the buffer. Relaxation responses persisted in vessels where an antioxidant had been included in the electrically stimulated buffer. Tissues stimulated without this protection did not relax on subsequent exposures to endothelium-dependent vasodilators. Scanning-electron microscopy of the tissues revealed significant endothelial damage (cell membrane pitting) in tissues exposed to electrical stimulation without antioxidant protection. These results suggest that electrical stimulation causes endothelial damage in isolated vascular preparations. This seemingly adverse effect proves to be a useful tool for removing the endothelium in studies of isolated vascular tissues.

Acetylcholine↗
PubMed1987

Potassium-induced relaxation in vascular smooth muscle of ground squirrels and rats.

This study was designed to assess differences in potassium-induced relaxation in two rodents, the Sprague-Dawley albino rat and the 13-lined ground squirrel, Citellus tridecimlineatus. Femoral arteries from both species were cut into helical strips for isometric force recording. After norepinephrine-induced contraction in potassium-free solution, the arterial strips relaxed in response to the introduction of potassium (0.25-20 mM) into the bath. Potassium-induced relaxation was greater in rat than ground squirrel arteries. The concentrations required to induce half-maximal relaxation were approximately 2.5 mM for both species. Potassium-induced relaxation varied with the duration of incubation in potassium-free solution, and with the contractile magnitude induced by varying norepinephrine concentrations. Ouabain inhibited potassium-induced relaxation, with the ground squirrel showing greater sensitivity to the cardiac glycoside than did the rat. Acute cooling (from 37 to 17 degrees C) caused a reduction of the contractile response to norepinephrine in rat arteries, whereas those taken from ground squirrels maintained contractions at, or above, those attained at 37 degrees C. In addition, potassium-induced relaxation in ground squirrel vessels was more sensitive to inhibition by cold than it was in those from the rat. The results show that the characteristics of potassium-induced relaxation (ouabain and temperature sensitivity, magnitude of response, etc.) are species related (ground squirrel vs. rat).

Animals↗
PubMed1987

Increased vasodilator responses to acetylcholine in psychosocial hypertensive mice.

Responsiveness to endothelium-dependent (acetylcholine and A23187) and endothelium-independent (nitroprusside and 8-bromo cyclic guanosine 3',5'-monophosphate [cGMP]) vasodilators was examined in two vascular preparations from hypertensive and normotensive mice. CBA Agouti mice were made hypertensive by exposure to social stress in a complex population cage. After 2 months, the hindquarter vascular bed was pump-perfused at a constant flow with plasma substitute to evaluate changes in perfusion pressure, and helical strips of aorta were suspended in muscle baths for measurement of isometric force generation. Tissues were treated with methoxamine to induce contractile tone. Threshold dilator responses to acetylcholine were elicited at a significantly lower dose in the hindquarters of hypertensive mice than in those from normotensive mice, indicating increased vasodilator sensitivity. In contrast, vasodilator responsiveness to nitroprusside in hindquarters of hypertensive mice did not differ from that in hindquarters of normotensive mice. Aortas from hypertensive mice were more sensitive (lower ED50) to the relaxant effects of acetylcholine and A23187 than those from normotensive mice. The relaxant effects of nitroprusside and 8-bromo cGMP on aortas from hypertensive mice were not significantly different from those in normotensive aortas. Aortic strips that had been rubbed on the lumen surface with a wooden stick did not relax to acetylcholine or A23187. In aortas that were not initially contracted with methoxamine, acetylcholine and A23187 caused small contractions from baseline. The magnitude of these contractile responses were potentiated after removal of the endothelium, and the potentiation was greater in aortas from hypertensive mice. These results demonstrate an increased responsiveness to endothelium-dependent vasodilators in this psychosocial model of hypertension.

Acetylcholine↗
PubMed1987

Vascular responsiveness to serotonin metabolites in mineralocorticoid hypertension.

This study characterizes vascular responsiveness to serotonin and its metabolites and to several monoamines that are structurally related to serotonin in deoxycorticosterone acetate (DOCA)-salt hypertension. Mesenteric arteries from normotensive and hypertensive rats were excised and cut into helical strips for isometric force recording. Dose-response curves to serotonin in arteries from hypertensive rats were shifted significantly to the left compared with those in arteries from normotensive rats (ED25: DOCA-treated = 2.4 X 10(-8) M; control = 17.1 X 10(-8) M). Contractile responses to 5-hydroxyindole acetic acid and 5-hydroxytryptophol were greater in mesenteric arteries from hypertensive rats, whereas reactivity to 5-methoxytryptamine and melatonin in arteries from hypertensive rats did not differ from that in arteries from normotensive rats. Mesenteric arteries from both rat groups were unresponsive to the serotonin metabolite N-acetylserotonin. Contractile responses to 5,6-dihydroxytryptamine and 6-hydroxytryptamine were greater in mesenteric arteries from hypertensive rats, whereas responsiveness to 3-hydroxytryptamine in hypertensive arteries did not differ from normotensive values. Contractile responses to serotonin and its metabolites and to the structurally related monoamines were inhibited by the serotonergic antagonist ketanserin. These results demonstrate that vascular sensitivity to serotonin is increased in DOCA-hypertensive rats. Based on the experiments with serotonin metabolites and with other monoamines, the increased responsiveness to these compounds appears to be related to the structural location of hydroxyl and amine moieties.

5,6-Dihydroxytryptamine↗
PubMed1987

Enhanced vascular reactivity to protein kinase C activators in genetically hypertensive rats.

Recent studies suggest that phospholipid-sensitive, Ca2+-dependent protein kinase C participates in contractile responses of vascular smooth muscle. This study characterizes vascular reactivity to protein kinase C activators in stroke-prone spontaneously hypertensive rats (SHRSP) and normotensive Wistar-Kyoto rats (WKY). Helical strips of mesenteric arteries were mounted in organ chambers for measurement of isometric contractions (responses were normalized as a percentage of maximal force in response to 100 mM KCl; in SHRSP, 350 +/- 16 mg; in WKY, 335 +/- 21 mg). Arteries from SHRSP contracted faster and developed greater force than arteries from WKY (168 +/- 9% vs 143 +/- 3%) in response to the phorbol ester, 12-O-tetradecanoylphorbol-13-acetate. Arteries from SHRSP (0.6 X 10(-8) M) were more sensitive to the phorbol ester than those from WKY (2.2 X 10(-8) M), as indicated by the dose of the phorbol ester required to produce 50% of the maximal response to KCl. Additionally, SHRSP arteries were more sensitive to the contractile effects of mezerein, a non-phorbol ester activator of protein kinase C. Ca2+-free solution (1.0 mM EGTA) and verapamil (10(-7) M) caused relaxation (approximately -60%) of contractions in response to the phorbol ester (10(-6) M). Addition of 10(-6) M of the phorbol ester to arteries that were preincubated in Ca2+-free solution (1.0 mM EGTA for 30 minutes) elicited submaximal contractions (in SHRSP, 26 +/- 4%; in WKY, 38 +/- 7%). Upon addition of 1.6 mM Ca2+, arteries from SHRSP contracted faster (t1/2 = 2.7 +/- 0.6 minutes) than those from WKY (8.2 +/- 0.5 minutes).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗