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C Richer

Publications and source records attributed to C Richer.

121 records · Page 7Linked to original sources
PubMedDate not supplied

Survival, haemodynamics and cardiac remodelling follow up in mice after myocardial infarction.

1. In the present study, the time-course, over a 1 year period, of postischaemic dilated cardiomyopathy and/or development of congestive heart failure was investigated in mice in terms of survival and cardiac functional and structural characteristics. 2. C57BL/6 mice with myocardial infarction (MI mice; coronary ligation n = 78) or sham-operated animals (n = 45) were used and echocardiographic, haemodynamic and histomorphometric parameters were assessed at 3, 6 and 12 months post-MI. 3. At 12 months, the survival rate was 70% in MI mice. Left ventricular dysfunction was evidenced by a strong decrease in ejection fraction (EF; -48 and -53% at 6 and 12 months, respectively; both P < 0.05) and an increase in left ventricular end-diastolic pressure (+100% at both 6 and 12 months; both P < 0.05). There was no major worsening in cardiac function between 6 and 12 months, suggesting strong compensatory mechanisms. Cardiac remodelling was observed, characterized by strong left ventricular hypertrophy (+38 and +62% at 6 and 12 months, respectively; both P < 0.05) and dilatation (+53% at 6 months; P < 0.05), but collagen was not significantly increased. Significant correlations were found between EF (echocardiography) and dP/dtmax, between end-diastolic volume (echocardiography) and left ventricular internal perimeter (histomorphometry) and between left ventricular mass (echocardiography) and weight. 4. In conclusion, despite a high survival rate, the MI mouse model displays most of the hallmarks of postischaemic dilated cardiomyopathy and/or congestive heart failure, thus affording the necessary background for the subsequent evaluation of gene manipulation and/or drug effects. In addition, two-dimensional echocardiography appears to be a suitable tool for the long-term follow up of cardiac function and remodelling in this model.

Animals↗
PubMedDate not supplied

Perindopril, a new converting enzyme inhibitor: systemic and regional hemodynamics and sympathoinhibitory effects in spontaneously hypertensive rats.

The effects of a new converting enzyme inhibitor, perindopril (5 mg/kg p.o. q.d. for 8 days), on systemic and regional hemodynamics, as well as its interferences with the sympathetic nervous system at the cardiovascular level, were investigated in nonbinephrectomized and in binephrectomized spontaneously hypertensive rats (SHRs). Perindopril abolished plasma converting enzyme activity and lowered arterial blood pressure (BP) without affecting heart rate. Cardiac index (microspheres) was not drug affected; thus, the reduction in BP was due to a decrease in total peripheral resistance which was shown to be homogenous, since all investigated vascular resistances were reduced to the same extent. In nonbinephrectomized, pithed SHRs, perindopril decreased BP and renal and hindlimb vascular resistances (pulsed Doppler). In addition, perindopril exerted a sympathoinhibitory effect as evidenced by (a) a reduction in the systemic vasopressor and regional vasoconstrictor responses to the alpha 1-adrenoceptor agonist, cirazoline, and especially to the alpha 2-adrenoceptor agonist UK 14.304; and (b) a decrease in the systemic pressor and in the hindlimb vasoconstrictor responses to spinal cord stimulation. In binephrectomized, pithed SHRs, perindopril no longer decreased BP; however, whereas its sympathoinhibitory effect versus alpha-adrenoceptor agonists was abolished, that versus spinal cord stimulation persisted. These results indicate that (a) perindopril lowers BP in SHRs by a renal-dependent mechanism; (b) perindopril exerts in SHRs a sympathoinhibitory effect versus alpha-adrenoceptor agonists and spinal cord stimulation; (c) the sympathoinhibitory effect of perindopril versus alpha-adrenoceptor agonists is postjunctional and kidney dependent; and (d) the sympathoinhibitory effect of perindopril versus spinal cord stimulation is possibly prejunctional in its mechanism and does not require the presence of the kidneys.

Angiotensin I↗
PubMedDate not supplied

Characterization and mechanisms of the cardiovascular and haemodynamic alterations induced by scorpion venom in rats.

The scope of this work was to investigate the nature, chronology and mechanisms of the cardiovascular disorders induced by scorpion envenomation. Anaesthetized rats were instrumented for measurement of cardiac output (CO), renal (RBF) and muscular (HBF) blood flows (pulsed Doppler flowmetry), blood pressure, heart rate and dP/dt. Buthus occitanus venom (BO) was administered intravenously in the absence/presence of different pre-treatments. BO dose-dependently (150-300 microg/kg) increased blood pressure, dP/dt, total peripheral (TPR), renal (RVR) and muscular (HVR) vascular resistances, and decreased CO, RBF and HBF. Recovery occurred after 150 but not after 300 microg/kg. BO, 600 microg/kg, produced qualitatively similar effects but arrhythmias developed and mortality increased. Pre-treatment with phentolamine prevented the rises in TPR, RVR, HVR and blood pressure and the decreases in CO, RBF and HBF induced by BO, 300 microg/kg. Pre-treatment with propranolol prevented the rise in dP/dt and the occurrence of arrhythmias and limited the rise in RVR and the drop in RBF induced by BO, 300 microg/kg. Phentolamine, propranolol and their combination also prevented BO, 600 microg/kg-induced mortality. Other pre-treatments (bosentan, losartan, diltiazem, mepyramine) were almost ineffective vs. BO effects. Finally, BO, 300 microg/kg, induced a 30-40-fold increase in plasma epinephrine and norepinephrine levels, but no change in plasma endothelin-1 levels. Thus in anaesthetized rats, the pattern of the cardiac and systemic and regional haemodynamic effects of BO is typically that of and results from catecholamine outpouring-induced alpha- and beta-adrenoceptor stimulation.

Animals↗
PubMedDate not supplied

Effects of captopril and enalapril on regional vascular resistance and reactivity in spontaneously hypertensive rats.

The present study compares the effects of short-term treatments with captopril and enalapril, administered in equipotent antihypertensive doses, on the regional vascular resistances and on the regional vascular responsiveness to vasopressor agents of adult spontaneously hypertensive rats (SHRs). Three groups of animals were treated by gavage with captopril (100 mg/kg), enalapril (25 mg/kg), or distilled water for 8 days. Arterial blood pressure (BP), heart rate (HR), plasma renin concentration (PRC), and plasma converting-enzyme activity (CEA) were measured. Cardiac index (CI), total peripheral resistance (PR), and organ flow distribution were determined using microspheres. Renal and mesenteric vascular responsiveness to vasopressor agents was evaluated by continuous measurement of renal and mesenteric blood flows with miniaturized pulsed Doppler flow probes. Data showed that in the anesthetized SHR the two drugs induced similar reductions in BP, PR, and HR, without affecting CI. They simultaneously produced a strong converting-enzyme inhibition as evidenced by the suppression of angiotensin I effects accompanied by a potentiation of angiotensin II responses, a reduction in CEA, and an increase in PRC. Organ flows were similarly and homogeneously increased, especially in the kidneys, in both treated groups. Norepinephrine (NE) vasoconstrictor responses were abolished in the mesenteric vascular bed by both drugs, but in the renal, NE responses although completely abolished by captopril were only partially reduced by enalapril. It thus appears that diminished vascular responsiveness to NE, especially in the case of captopril, is probably involved along with converting-enzyme inhibition in the antihypertensive action of converting enzyme inhibitors (CEI), the mechanism of the difference between captopril and enalapril remaining still speculative.

Animals↗
PubMedDate not supplied

Influence of captopril and enalapril on regional vascular alpha-adrenergic receptor reactivity in SHR.

The effects of short-term oral treatment with captopril and enalapril (two angiotensin-I-converting-enzyme inhibitors [ACEIs] that were administered in equipotent antihypertensive doses) on the systemic vasopressor response and on the renal, mesenteric, and hindlimb vascular responses to cirazoline and UK-14,304 (alpha 1- and alpha 2-adrenergic receptor-specific agonists, respectively) were investigated in adult pithed spontaneously hypertensive rats (SHR) of the Okamoto-Aoki strain. In the nonbinephrectomized animal, captopril and enalapril reduced to the same extent the systemic blood pressure and renal and hindlimb vascular resistances. They also decreased to the same extent systemic pressor and regional vasoconstrictor responses to cirazoline and UK-14,304, especially in the renal and mesenteric vascular beds. Simultaneously, the effects of angiotensin I and angiotensin II on the pressor response were abolished and almost not modified. In the binephrectomized animals, captopril and enalapril no longer reduced the systemic blood pressure and regional vascular resistances, but whereas the sympathoinhibitory effect of captopril vs the systemic pressor and regional vasoconstrictor responses to cirazoline and UK-14,304 persisted, those of enalapril disappeared.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin II↗
PubMedDate not supplied

Antihypertensive drugs in the stroke-prone spontaneously hypertensive rat.

The stroke-prone spontaneously hypertensive rat (SHR-SP) is an experimental model that has been widely used to investigate the potential preventive effects vs stroke and mortality of numerous antihypertensive agents. Among the latter, angiotensin I-converting enzyme inhibitors, angiotensin II AT1-receptor blockers and calcium antagonists have proven to be very effective. The mechanisms involved in their beneficial effects include limitation of the age-related alterations of large cerebral arteries' functional parameters, prevention of fibrinoid necrosis formation in cerebral arterioles and, to a lesser extent, limitation of the blood pressure rise.

Animals↗
PubMedDate not supplied

Evidence that 5-HT2 receptors mediate the pressor effect of 8-OH-DPAT in the spinally pithed rat.

The aim of the present experiments was to investigate whether 8-OH-DPAT, a selective 5-HT1A agonist, could induce vasoconstriction in vivo and, if so, the type of receptors functionally involved. Dose-response curves to bolus intravenous doses of 8-OH-DPAT were established in anesthetized spinally pithed rats. The peak increase in the mean arterial pressure-log dose (microgram/kg) relationship was fitted to a sigmoidal logistic equation. In the control group, the dose-response curve was steep. The half maximal dose was 743 micrograms/kg. The maximal response was 43 mmHg. Ketanserin, a potent 5-HT2 and alpha 1-adrenoceptor antagonist (0.25 mg/kg), essentially abolished the effect of 8-OH-DPAT (maximal rise = 6 mmHg). Ritanserin (0.25 mg/kg) and LY 53857 (100 micrograms/kg), which have relatively weak affinity for alpha 1-adrenoceptors, also markedly reduced the pressor action of 8-OH-DPAT (maximal rise 17 and 9 mmHg). Prazosin, an alpha 1-adrenoceptor antagonist, slightly reduced the maximal response to 8-OH-DPAT (22% reduction). Adrenalectomy did not affect the pressor response (42 mmHg). This excluded a contribution of an acute release of adrenaline in the blood pressure elevation. (-)Propranolol (5 mg/kg), a beta-blocker with a 5-HT1A antagonistic action, affected the 8-OH-DPAT-induced blood pressure elevation (37% reduction). However, two other beta-blockers with a similar 5-HT1A antagonistic property, (-)pindolol (5 mg/kg) and (+/-)cyanopindolol (10 mg/kg), did not (maximal rise 44 and 39 mmHg). Finally, 8-OH-DPAT dose-dependently increased local vascular resistances, with a regional profile similar to that of 5-HT, with the hindquarter being the most sensitive vascular bed. Ketanserin also prevented the vascular effects of 8-OH-DPAT. Our pharmacological analyses of the vascular action of 8-OH-DPAT in the spinally pithed rat indicated that this drug caused dose-related increases in blood pressure. This effect depended on a rise in peripheral vascular resistance, particularly in the hindquarter and kidney beds. Our data suggest that the 5-HT1A agonistic property of 8-OH-DPAT cannot account for this pressor effect which seems to depend on the activation of the vascular 5-HT2 receptor.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMedDate not supplied

[Potassium channel activators: from pharmacology to therapeutics].

Potassium channels activators (PCA) are drugs which open or prolong the open state duration of potassium channels. Hence they promote potassium efflux, hyperpolarize the cell membrane, thus preventing intracellular penetration of calcium through the voltage-dependent calcium channels. The resulting decrease in intracellular free calcium concentration induces relaxant effects in smooth muscle cells (vessels, bronchi, bladder, etc.) which are the rationale for the present and future therapeutic indications of PCA, namely hypertension, asthma, etc. In animals, PCA produce vasodilating, hypotensive and antihypertensive effects, accompanied by tachycardia and stimulation of the renin-angiotensin system. The regional vasodilator profile of PCA is heterogeneous and their hypotensive properties are antagonized only by glibenclamide, an antagonist of ATP-dependent potassium channels. In patients, only pinacidil, minoxidil and diazoxide are presently used as antihypertensive drugs.

Antihypertensive Agents↗
PubMedDate not supplied

[Nicardipine: experimental antihypertensive action and interactions with the alpha-adrenergic sympathetic system].

The antihypertensive properties of nicardipine have been studied in various experimental models of hypertension. Furthermore, the possible contribution of the nicardipine-alpha-adrenergic system interaction to the drug's antihypertensive effect has been investigated. In the conscious normotensive rat, nicardipine (10 and 30 mg/kg, orally) reduces arterial blood pressure (by about 25%) and increases heart rate; these effects are maximal one hour after drug administration and disappear within 4 to 6 hours. In the renovascular hypertensive rat and in the Grollman hypertensive dog, nicardipine (3 mg/kg, orally) significantly decreases blood pressure. Simultaneously, heart rate is increased in the dog but is not significantly modified in the rat. In the conscious adult spontaneously hypertensive rat (SHR), nicardipine administered either as a bolus, or by intra arterial perfusion (1, 5, 12.5 micrograms/kg/min during 30 min), or orally (10, 30 mg/kg) dose-dependently decreases blood pressure and increases heart rate. In the pithed SHR, nicardipine decreases systemic pressor and regional (kidney, mesentery, hindlimb) vasopressor responses to M7, an alpha 2-adrenoceptor specific agonist, but does not affect those to cirazoline, an alpha 1-adrenoceptor specific agonist. However, there is no evidence for an involvement of this alpha 2-sympathoinhibitory effect in the blood pressure lowering action of nicardipine. In conclusion, in the different investigated experimental models of hypertension, nicardipine exerts a potent but short-lasting antihypertensive effect generally accompanied by a reflex tachycardia and a systemic and regional vascular alpha 2-sympathoinhibitory action.

Adrenergic alpha-Agonists↗
PubMedDate not supplied

Cimetidine does not alter free unchanged captopril pharmacokinetics and biological effects in healthy volunteer.

The effects of cimetidine (single or repeated administration) on free unchanged captopril plasma levels, pharmacokinetic parameters and plasma converting enzyme inhibitory effects have been investigated in normal healthy volunteers. Cimetidine affected neither captopril pharmacokinetic parameters nor its biological effects, suggesting that no change in captopril dosing is necessary when cimetidine is co-administered.

Adult↗
PubMedDate not supplied

[Nicardipine: vascular compliance and development of genetic hypertension in the SHR rat].

The potential preventive effects of nicardipine (100 mg/kg q.d., orally, for 6 weeks, starting at the 6th week of age) on genetic hypertension development (GHD) have been investigated in young SHRs. Furthermore, at the end of the treatment period, segments of mesenteric arteries were isolated in order to determine their vascular compliance and reactivity to noradrenaline and the total proteins content and the amount of DNA in the vascular wall. At the end of the treatment period and 20 hours after the last drug administration, nicardipine exhibited no preventive effects against GHD but heart rate was lower in treated than in control animals. Mesenteric vascular compliance was not treatment-affected but the maximal contractile response of the vessels to noradrenaline was slightly decreased. Finally, total proteins and DNA contents of the vascular wall were unchanged. It thus appears that there is a striking parallelism between nicardipine's lack of effects on resistance vessels' compliance and vascular total proteins and DNA contents on the one hand and the drug's inability to oppose GHD in young SHRs on the other.

Animals↗
PubMedDate not supplied

Bromocriptine and genetic hypertension development in young spontaneously hypertensive rats.

The effects of bromocriptine (BRC; 20 mg X kg-1, b.i.d., orally) on genetic hypertension development (GHD), cardiovascular hemodynamics, regional vascular reactivity to vasopressor agents and biological parameters have been investigated in spontaneously hypertensive rats (SHRs) treated from their 4th to 20th weeks of age. BRC only partially opposed GHD and this was due to a limitation of the progressive increase in peripheral resistance which normally develops in SHRs with ageing since simultaneously cardiac index was not modified. Renal blood flow was increased and renal and mesenteric vascular responsiveness to norepinephrine was reduced. BRC almost completely suppressed prolactin plasma levels and slightly reduced epinephrine and norepinephrine plasma levels. Plasma Na+ and urinary volume and ADH values were not modified. The discrepancy between the favourable antihypertensive profile of BRC and its limited preventive effects against GHD remains to be elucidated.

Aging↗