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D Henrion

Publications and source records attributed to D Henrion.

66 records · Page 4Linked to original sources

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

Chronic decrease in flow contributes to heart failure-induced endothelial dysfunction in rats.

Chronic heart failure (CHF) impairs endothelium-dependent, nitric oxide (NO)-mediated dilation. This decreased dilation may be partly secondary to the chronic decrease in blood flow, but this hypothesis has not yet been tested. Thus, we assessed whether a localized, chronic increase in blood flow in vivo reverses endothelial dysfunction of small arteries in rats with CHF. Two months after coronary artery ligation or sham surgery, second-order side branches of the superior mesenteric artery were ligated in order to obtain persistently elevated blood flow (HF) in the adjacent first-order side branch compared with normal vessels (NF). One month later, responses to acetylcholine and flow-mediated vasodilatation (FMD) were assessed in vitro in an arteriograph. Chronic heart failure induced a decrease in mesenteric blood flow (374 +/- 25 and 305 +/- 27 micro L/min for sham and CHF, respectively; P < 0.05). Neither CHF nor the chronic increase in flow affected the responses to acetylcholine. Chronic heart failure decreased FMD (maximal response in sham and control 34 +/- 6 and 13 +/- 4%, respectively; P < 0.05). Chronic increases in blood flow did not modify FMD in sham, but restored FMD in CHF rats (28 +/- 4%; P < 0.05 vs CHF NF). The restored response was abolished by an inhibitor of NO synthesis (N(G)-nitro-l-arginine). Chronic heart failure did not affect the abundance of mesenteric endothelial NO synthase (eNOS) mRNA. A chronic increase in flow significantly increased the abundance of eNOS mRNA in sham rats, but only moderately and non-significantly in CHF rats. Thus, endothelial dysfunction of small arteries in CHF appears to be largely the consequence of the chronic decrease in flow.

Acetylcholine↗

Angiotensin II type 1 receptor gene polymorphism is associated with an increased vascular reactivity in the human mammary artery in vitro.

A gene polymorphism of the angiotensin II (AII) type 1 receptor has been described previously (A to C transversion at position 1166). Besides the epidemiological studies needed to determine a possible relationship between the polymorphism and some cardiovascular diseases, no study has been conducted to determine the impact of the polymorphism on vascular functions. At subthreshold concentrations, within the physiological range, AII potentiates alpha-adrenergic-dependent vascular tone. We investigated phenylephrine-induced tone and its amplification by AII (10 pmol/l) in human internal mammary artery rings mounted in organ baths. We performed concentration-response curves to phenylephrine (0.1-100 micromol/l) before and after pretreatment with AII (10 pmol/l). Patients had the genotype AA (n = 20) or the A to C transversion (AC/CC, n = 30). Contractions to phenylephrine (0.1-100 micromol/l) were significantly higher in rings from AC/CC than from AA patients (maximum response: 1.47+/-0.07 vs. 1.22+/-0.06 mN/mg, p < 0.001). AII (10 pmol/l) induced a significant potentiation of phenylephrine-induced contraction (e.g. 58.9% increase in tone with 1 micromol/l phenylephrine, p < 0.001) which was significantly lower in the AC/CC than in the AA group (46+/-9 vs. 66+/-7% with 1 micromol/l phenylephrine, p < 0.01). Contractions to AII (1 or 100 nmol/l) were not significantly affected by the genotype. Although the study was performed in arteries from patients with a coronary artery disease, these changes in vascular reactivity might be of interest in the understanding of the relationship between a possible higher probability of cardiovascular disorder and the genetic polymorphism of the AII type 1 receptor.

Aged↗

Magnitude of flow-induced contraction and associated calcium influx in the rabbit facial vein is dependent upon the level of extracellular sodium.

Intraluminal flow can cause both dilation or constriction of small arteries, depending on the level of tone. Both responses are specifically modulated in the same way by small changes in extracellular Na+ ([Na+]e). We have investigated the effect of changes in [Na+]e on the level of contraction induced by a standard flow of physiological salt solution in ring of segments of the rabbit facial vein and on the associated 45Ca2+ influx and net uptake. Decreasing [Na+]e by 20% reduced the response to flow by 58%, and increasing it by 20% augmented the flow response by the same extent. There is a linear relationship between the level of the flow-induced contraction and [Na+]e over the range 120-180 mM. An alteration in [Na+]e of 10 mM corresponds to a 20% change in flow-induced contraction. This relationship is quantitatively the same as that previously reported for the rabbit ear resistance artery [10]. Histamine (1 microM)-induced tone was not affected by changes in [Na+]e within the range 75-180 mM. 45Ca2+ influx and net uptake per unit force developed in response to flow were unaffected by these changes in [Na+]e. The flow-induced contraction of the vein was selectively, in comparison to that due to histamine, attenuated by amiloride, methyl-isobutyl-amiloride and monensin. It is argued that the observation that flow-induced contraction, caused by small alterations in extracellular sodium concentration, is not associated with changes in calcium uptake per unit force is consistent with an extracellular flow sensor.(ABSTRACT TRUNCATED AT 250 WORDS)

Amiloride↗

Intraluminal flow preferentially increases net sodium uptake in the rabbit facial vein.

The infusion of physiological salt solution into the lumen of ring segments of the isolated rabbit facial vein induces an increase in vessel wall tone. Changes in 22Na+ and 45Ca2+ net uptake as well as 22Na+ unidirectional efflux in response to flow in this vessel were compared to the response to histamine (1 microM) and to angiotensin II (0.1 microM). 22Na+ net uptake per unit force developed in response to flow was 7.9-fold greater than that for histamine (1 microM) and twice that for angiotensin II (0.1 microM). In comparison, 45Ca2+ net uptake per unit force in response to flow, histamine and K+ were similar. Flow-induced contraction and the related 45Ca2+ and 22Na+ net uptake were decreased by amiloride (30 microM) and methyl isobutyl amiloride (30 microM) without changes in 45Ca2+ or 22Na+ net uptake per unit force. Ouabain (10 microM) enhanced flow-induced contraction and the related 22Na+ net uptake. Both ouabain (10 microM) and Bay K 8644 (1 microM) increased flow-induced contraction and the related 45Ca2+ net uptake whereas they decreased the 45Ca2+ net uptake per unit force. Flow, histamine and angiotensin II increased the unidirectional efflux of 22Na+. This increase in 22Na+ unidirectional efflux was attenuated by ouabain (10 microM). These experiments demonstrate that the increases in wall force due to flow, histamine and angiotensin II are associated with increases in 22Na+ net uptake and unidirectional efflux. Flow preferentially promotes the entry of Na+, compared to histamine and angiotensin II.

Angiotensin II↗