Biomedical subjects

D Henrion

Publications and source records attributed to D Henrion.

12 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

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

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

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

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

Differences between the in vitro vasoconstrictor responses of the tail artery to potassium and norepinephrine between spontaneously hypertensive, renovascular hypertensive, and various strains of normotensive rats.

Isolated tail arteries removed from spontaneously hypertensive, renovascular hypertensive, or various strains of normotensive rats were perfused/superfused with norepinephrine or potassium, or subjected to electrical field stimulation. Responses in spontaneously hypertensive and outbred normotensive rat tail artery preparations were similar. Tail artery segments from renovascular hypertensive or normotensive rats of the inbred Wistar-Kyoto strain showed smaller responses to all three stimuli. Thus, in certain in vitro arterial preparations, the apparent increase in vascular reactivity observed when comparing spontaneously hypertensive rats with inbred Wistar-Kyoto rats may be due to a decrease in vascular reactivity in the Wistar-Kyoto rat strain.

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↗

PubMed1990

In vitro vasoconstriction induced by calcium in renovascular hypertensive or old rats.

We studied the changes in calcium-induced vasoconstriction in isolated tail arteries from young (2 months) and old (12 months) normotensive, and young renovascular hypertensive rats (3 months old, with unilateral renal artery clipping at 6 weeks), pretreated with reserpine. The tail artery was removed and perfused/superfused with either a high potassium Krebs depolarizing solution or Krebs solution plus phenylephrine. Concentration-response curves to calcium were produced. Old rats had a low plasma renin activity and their depolarized tail arteries showed a weak vasoconstrictor response to calcium. Renovascular hypertensive rats had a high mean blood pressure and plasma renin activity. Responses of their depolarized tail arteries to calcium were greater. Responses to calcium in tail arteries perfused with phenylephrine were similar in all groups. We conclude that age and renovascular hypertension produce opposite changes in vasoconstriction induced by calcium in depolarized tail arteries.

Aging↗

PubMed1990

Vascular calcium overload produced by administration of vitamin D3 and nicotine in rats. Changes in tissue calcium levels, blood pressure, and pressor responses to electrical stimulation or norepinephrine in vivo.

Increased calcium content of cardiovascular tissues is a phenomenon common to natural aging and various pathological conditions such as hypertension and arteriosclerosis. We investigated an accelerated cardiovascular calcium overload model in young rats produced by treatment with a single dose of vitamin D3 (300,000 IU/kg, i.m.) followed by up to 4 days of twice daily doses of nicotine (25 mg/kg, p.o.). Large increases in the calcium content of the aorta, kidneys, and myocardium but not in the liver or brain were seen. The magnesium content of these tissues was not modified. On the day following the last nicotine injection, there was marked cardiovascular calcium overloading, the aortic calcium level increasing by up to nine times that of controls. The animals had lower body weights, however, and there was a significant degree of mortality (up to 42%). Signs of kidney failure were evident; the blood urea level, for instance, was doubled. If rats were allowed 13 or 180 days to recover, they showed normal growth and kidney function; aortic calcium overload was still pronounced: 16- and 7-fold increases, respectively. Cardiovascular function in recovery animals was characterized by a doubling of pulse pressure. Dose-response curves following noradrenergic stimulation were shifted to the right after 13 (but not after 180) days recovery. Arterial norepinephrine content doubled. The chronic effects of hypervitaminosis D plus nicotine may produce a useful model for the study of the physiological and/or pharmacological consequences of calcium overload.

Aging↗

PubMed1989

Blood pressure, the renin-angiotensin system and neurogenic vasoconstriction in pithed rats.

The influence of changing baseline blood pressure by various means, both related or unrelated to the renin-angiotensin system, on the pressor responses to spinal cord stimulation has been examined in the pithed rat. Mean arterial pressure and neurogenic vasoconstriction were higher in pithed rats with intact kidneys (2-kidney rats) than in nephrectomized pithed rats. Increasing blood pressure by infusion of vasopressin increased the pressor response to nerve stimulation in both 2-kidney and nephrectomized pithed rats. Decreasing blood pressure produced by administration of enalaprilat or hydralazine in 2-kidney pithed rats or by administration of hydralazine in nephrectomized pithed rats, decreased the pressor responses to nerve stimulation. Our results showed a positive correlation between the mean arterial blood pressure and the response to nerve stimulation in pithed rats. Therefore, we conclude that the pithed rat is an animal model which should be used with caution to study the interaction between the sympathetic nervous system and drugs which change baseline blood pressure.

Animals↗