Biomedical subjects

C Capdeville-Atkinson

Publications and source records attributed to C Capdeville-Atkinson.

9 recordsLinked to original sources

PubMed1992

[Cerebral blood flow. Changes in regulation with aging].

In subjects without cardiovascular or neuronal diseases ageing does not seem to be accompanied by a significant fall in global cerebral blood flow at rest. Yet non-negligible changes in cerebral blood flow rate can be demonstrated by haemodynamic or metabolic stimuli. Several intra- and extracranial vascular mechanisms may be involved in these changes. During ageing, a decrease of carotid artery compliance due to parietal calcium deposition might be an important factor in the disturbance of cerebral blood flow regulatory mechanisms.

Aging↗

PubMed1992

Haemodynamic effects of a new dihydropyridine calcium entry blocker, S-12968-(-), in a rat model of cardiovascular calcium overload.

1. The haemodynamic effects of S-12968-(-), a new dihydropyridine calcium entry blocker (enantiomer of S-11568), were compared with those of the stereoisomer, S-12967-(+), nifedipine, and sodium nitroprusside. 2. A first experiment was performed in conscious, young male rats chronically implanted with femoral artery and vein cannula and repeated in rats previously treated with vitamin D3 and nicotine. Such treatment produces marked vascular calcium overload, especially of the compliance arteries, with no overt sign of toxicity as far as can be judged from the plasma profile. 3. In conscious rats the hypotensive effects of S-12968-(-), nifedipine and sodium nitroprusside were of similar potency. The falls in blood pressure produced by nifedipine and sodium nitroprusside were accompanied by reflex tachycardia which was less marked in the vascular calcium overload model. S-12968-(-) did not induce reflex tachycardia. S-12967-(+) increased blood pressure in both models. 4. A second experiment was performed in open-chest pentobarbitone-anaesthetized rats with electromagnetic flowprobes on the ascending aorta. In controls the falls in blood pressure produced by low doses (0.1 and 0.3 mg kg-1, i.v.) of S-12968-(-) were accompanied by falls in total peripheral resistance. The higher dose (1 mg kg-1, i.v.) of S-12968-(-) produced no change in total peripheral resistance, and in rats pretreated with vitamin D3 and nicotine, cardiac output fell. 5. In conclusion, S-12968-(-) appears to have a dual action and to lower blood pressure at higher doses at least in part by a cardiac effect. This phenomenon is more pronounced in rats pretreated with vitamin D3 and nicotine.6. S-12967-(+) resembles a calcium channel activator in this model.

Animals↗

PubMed1992

Chronic antihypertensive treatment with captopril plus hydrochlorothiazide improves aortic distensibility in the spontaneously hypertensive rat.

1. Adult male spontaneously hypertensive rats (SHR) were given captopril plus hydrochlorothiazide mixed in the diet for 10 weeks. Calculated daily doses were 44 mg kg-1 per day for captopril, and 22 mg kg-1 per day for hydrochlorothiazide. Separate groups received captopril or hydrochlorothiazide alone, at similar doses, or no treatment. A final group of WKY normotensive rats received no drug. 2. Systolic arterial blood pressure, measured at regular intervals throughout the 10 weeks' period was lowered but not normalized, in groups receiving either captopril plus hydrochlorothiazide, or captopril alone, but not in the group receiving hydrochlorothiazide alone. 3. Following pentobarbitone anaesthesia, systolic arterial blood pressure, measured in the femoral artery, was found to be lower in all treated groups, but the greatest effect was observed in SHR previously treated with captopril plus hydrochlorothiazide. Aortic pulse wave velocity was also lower in treated SHR, and once again the greatest decrease was observed in the group previously treated with captopril plus hydrochlorothiazide. 4. Following pithing, systolic arterial blood pressures were similar in all SHR groups. Aortic pulse wave velocity was lower in pithed rats previously treated with captopril and hydrochlorothiazide. 5. In conclusion, antihypertensive treatment of SHR produces falls in blood pressure and pulse wave velocity, an indicator of aortic distensibility. Results in pithed rats suggest that treatment with the combination of captopril plus hydrochlorothiazide may increase aortic distensibility independently of blood pressure.

Animals↗

PubMed1992

Effect of chronic treatment with the calcium entry blocker, isradipine, on vascular calcium overload produced by vitamin D3 and nicotine in rats.

Treatment of young rats with vitamin D3 and nicotine produced a 35-fold increase in the calcium content of the aorta and a 4-fold increase in the calcium content of the mesenteric arterial bed. Blood pressure was not modified. In vitro, aortic rings and mesenteric arterial bed preparations from such animals showed diminished vasoconstrictor responses to norepinephrine. After precontraction with norepinephrine, the endothelium-dependent vasodilator, carbachol, produced vasorelaxation. This latter effect was attenuated in aortic rings and mesenteric arterial bed preparations from animals previously treated with vitamin D3 and nicotine, but the vasodilator effect of sodium nitroprusside (which is independent of the endothelium) was unchanged. Prolonged treatment with the calcium entry blocker, isradipine, at a dose (1 mg/kg, i.p.) which had no effect on blood pressure, prevented calcium overload of the mesenteric arterial bed, but did not modify aortic calcium overload. Isradipine treatment had no effect on vasoconstrictor responses to norepinephrine in vitro. Such treatment did, however, restore the endothelium-dependent vasodilator effect of carbachol in the mesenteric arterial bed (but not in aortic rings). In conclusion, in a rat model of vascular calcium overload produced by administration of vitamin D3 plus nicotine, chronic treatment with a low dose of the calcium entry blocker, isradipine, restored the endothelium-dependent vasorelaxant effect of carbachol in the mesenteric arterial bed, but not in the aorta.

Animals↗

PubMed1992

[Effect of isosorbide dinitrate on vasomotricity-cytosolic calcium coupling during aging in the rat].

Simultaneous measurement of vasomotricity and variations of cytosolic calcium concentrations (mobilisation of intracellular calcium) on a preparation of a normotensive Wistar rat caudal artery allowed analysis of the vasomotricity-cytosolic calcium coupling with respect to age and after administration of isosorbide dinitrate. Vasomotricity was evaluated from changes in perfusion pressure (delta P) of arterial segments perfused at a steady flow state. These segments were exposed to a fluorescent probe, fura 2, the variations of the intensity of emission of which, at wave lengths of 340 and 380 nm, reflect variations in cytosolic calcium concentration (delta R%). The "efficacy" of the vasomotricity-cytosolic calcium coupling was estimated from the delta P/delta R% ratio. In the rat, ageing is accompanied by a reduction in vasomotricity and efficacy of the coupling during noradrenalin stress testing. However, these two parameters recorded during contractions induced by the calcium in a depolarising medium do not change with age. Isosorbide dinitrate reduces vasoconstriction and the delta P/delta R% ratio during noradrenalin stimulation in the young rat. The effect is less pronounced in older rats. Isosorbide dinitrate also reduced the vasomotricity and efficacy of coupling but to a lesser degree during vaso-constriction induced by the calcium in a depolarising medium, without changing the mobilisation of intracellular calcium irrespective of the age of the animals. In conclusion, ageing seems to affect the vasomotricity-cytosolic calcium coupling mainly during receptor stimulation (noradrenalin) rather than during depolarising stimulation (calcium in a depolarising medium). Isosorbide dinitrate acts mainly on the same depolarising stimulation, independent of age.

Aging↗

PubMed1991

The role of endogenous norepinephrine release in potassium-evoked vasoconstriction of the rat tail artery.

Potassium-containing solutions are often used to study the sequence of events leading from excitation to vasoconstriction. In densely innervated vessels, such as the rat tail artery, potassium-induced vasoconstriction may be mediated via smooth muscle depolarization and release of endogeneous norepinephrine. The relative contribution of these two mechanisms--a 'direct' depolarization of the vascular smooth muscle cell membrane, and an 'indirect' sympathomimetic action--to the vasoconstrictor response was studied in the present paper. Perfusion/superfusion of the rat tail artery in vitro with potassium-containing solutions had different effects depending on the concentration used. A change in potassium concentration from 4.7 to 20 mM had no effect on either perfusion pressure or norepinephrine overflow. From 30 to 70 mM, potassium produced increasing amounts of norepinephrine overflow. Experiments with phentolamine and reserpine showed that this norepinephrine overflow contributed for up to half of the vasoconstrictor response observed. A second norepinephrine-independent mechanism was also involved but the latter appeared to be incapable of producing sustained contraction. At concentrations of potassium above 50-70 mM, the results of experiments with (+/-)-propranolol suggest that the norepinephrine released by potassium has a beta-adrenoceptor-mediated vasorelaxant effect.

Animals↗

PubMed1991

Decrease in endothelium-dependent relaxation in the mesenteric arterial bed following vascular calcium overload produced by vitamin D3 and nicotine in rats.

Treatment of young rats with vitamin D3 plus nicotine, which has been proposed as a model of cardiovascular calcium overload, produced an increase in the calcium content of the mesenteric arterial bed and lowered in vitro vasoconstrictor responses to norepinephrine and serotonin. Attenuation of the vasoconstriction induced by norepinephrine by the endothelium-dependent vasodilators, carbachol and histamine, was diminished, but the effects of sodium nitroprusside and papaverine were unchanged. The vitamin D3 plus nicotine model may be useful for the study of the involvement of calcium overload in vascular endothelial dysfunction.

Animals↗

PubMed1991

Chronic treatment with the angiotensin I converting enzyme inhibitor, perindopril, protects in vitro carbachol-induced vasorelaxation in a rat model of vascular calcium overload.

1. Treatment of young rats with vitamin D3 plus nicotine produced 31 and 4 fold increases in the calcium content of the aorta and the mesenteric arterial bed, respectively. 2. Aortic rings and perfused mesenteric arterial beds from vitamin D3/nicotine-treated animals showed a diminished contractile response to noradrenaline in vitro. 3. In vascular preparations from vitamin D3/nicotine-treated animals, precontracted with noradrenaline, relaxation by the endothelium-dependent vasodilator, carbachol, was attenuated but responses to sodium nitroprusside were not modified. 4. Prolonged treatment with the angiotensin I converting enzyme inhibitor, perindopril, at a dose (1 mg kg-1) which did not significantly modify blood pressure, failed to prevent vascular calcium overload. 5. Perindopril treatment diminished noradrenaline-evoked vasoconstrictor responses of aortic rings in both groups, but restored responses in mesenteric arterial beds of vitamin D3/nicotine-treated rats. 6. Perindopril treatment also restored the maximal responses to carbachol of both aortic rings and mesenteric arterial beds of vitamin D3/nicotine-treated rats. 7. In conclusion, in the vitamin D3 plus nicotine model of calcium overload, reduced endothelial-mediated relaxation can be prevented by perindopril treatment.

Angiotensin-Converting Enzyme Inhibitors↗

PubMed1991

The consequences of aortic calcium overload following vitamin D3 plus nicotine treatment in young rats.

Treatment of young rats with vitamin D3 plus nicotine has been proposed as a model of cardiovascular calcium overload. This treatment produced a 20-35-fold increase in the calcium content of the aorta, a compliance vessel, and this increase was accompanied by a 1.6-fold elevation of pulse pressure. In aortic rings, the maximal inhibition by the endothelium-dependent vasodilator, carbachol, of vasoconstriction induced by noradrenaline decreased from 90% in controls to 61% in treated animals. There were significant correlations between aortic calcium content and pulse pressure and aortic calcium content and carbachol-induced relaxation. In conclusion, the vitamin D3 plus nicotine model may be useful for the study of the role of calcium overload in decreased arterial compliance coupled with endothelial injury.

Animals↗