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S Lahlou

Publications and source records attributed to S Lahlou.

At least 19 recordsLinked to original sources

Role of capsaicin-sensitive sensory nerves in mediation of the cardiovascular effects of the essential oil of croton zehntneri leaves in anaesthetized rats.

The essential oil of Croton zehntneri Pax et Hoffm. (EOCZ) contains anethole (42%) and estragole (46%), two isomers that share some chemical structural similarities with capsaicin. The present study investigated the cardiovascular effects of EOCZ and the role of capsaicin-sensitive sensory nerve fibres in the mediation of these effects in anaesthetized rats. 2. Intravenous bolus injection of EOCZ (1-20 mg/kg) elicited dose-dependent hypotension and bradycardia that were immediate and transient. Similar responses were also observed with anethole and estragole (both at 10 mg/kg). After cervical bivagotomy or perineural treatment of both cervical vagus nerves with capsaicin (250 mg/mL) to selectively block the conduction of sensory C-fibres, both cardiovascular responses to EOCZ (10 mg/kg) were abolished. 3. Like capsaicin, an epigastric retrograde intra-arterial injection of EOCZ (10 mg/kg, i.a.) into the femoral artery elicited a monophasic hypotensive response. This reflex response was blocked by either neonatal pretreatment with capsaicin (50 mg/kg, s.c.) or intrathecal injection of the substance P receptor antagonist RP 67580 (7.8 nmol, at the spinal level L5-L6), suggesting that it is mediated exclusively by substance P-containing primary afferent fibres. 4. The cardiovascular responses to EOCZ (10 mg/kg, i.v.) were also significantly reduced by the selective vallinoid TPRV1 receptor antagonist capsazepine (1 mg/kg, i.v.). 5. It is concluded that i.v. administration of EOCZ in anaesthetized rats elicits a capsaicin-like bradycardic and depressor reflex, which appears to be mediated by the activation of vallinoid TPRV1 receptors located on vagal sensory nerves. Like capsaicin, i.a. injection of EOCZ induces a spinally mediated sensory reflex.

Allylbenzene Derivatives↗

Essential oil of croton nepetaefolius and its main constituent, 1,8-cineole, block excitability of rat sciatic nerve in vitro.

1. The effects of the essential oil of Croton nepetaefolius (EOCN) and its major constituent, 1,8-cineole, on the compound action potential (CAP) of nerve were investigated. 2. Experiments were performed in sciatic nerves dissected from Wistar rats, mounted in a moist chamber and stimulated at a frequency of 0.2 Hz, with electric pulses of 100 micros duration at 20-40 V. Evoked CAP were displayed on an oscilloscope and recorded on a computer. The CAP control parameters were as follows: peak-to-peak amplitude 8.1 +/- 0.6 mV (n = 15); conduction velocity 83.3 +/- 4.2 m/s (n = 15); chronaxie 58.0 +/- 6.8 msec (n = 6); and rheobase 2.8 +/- 0.1 V (n = 6). 3. Lower concentrations of EOCN (100 and 300 microg/mL) and 1,8-cineole (153 and 307 microg/mL; i.e. 1 and 2 mmol/L, respectively) had no significant effects on CAP control parameters throughout the entire recording period. However, at the end of 180 min exposure of the nerve to the drug, peak-to-peak amplitude was significantly (P < 0.05) reduced to 27.4 +/- 6.7 and 1.7 +/- 0.8% of control values by 500 and 1000 microg/mL EOCN, respectively (n = 6), and to 76.5 +/- 4.4, 70.0 +/- 3.9 and 14.8 +/- 4.1% of control values by 614, 920 and 1227 microg/mL (i.e. 4, 6 and 8 mmol/L) 1,8-cineole, respectively (n = 6). Regarding conduction velocity, at the end of the 180 min exposure period, this parameter was significantly reduced to 85.8 +/- 7.3 and 48.7 +/- 12.3% (n = 6) of control values by 500 and 1000 microg/mL EOCN, respectively, and to 86.4 +/- 4.5 and 76.1 +/- 5.2% (n = 6) by 920 and 1227 microg/mL 1,8-cineole, respectively. Chronaxie and rheobase were significantly increased by the higher concentrations of both EOCN and 1,8-cineole. 4. It is concluded that EOCN and its main constituent 1,8-cineole block nerve excitability in a concentration-dependent manner, an effect that was totally reversible with 1,8-cineole but not with EOCN. This suggests that other constituents of EOCN, in addition to 1,8-cineole, may contribute to the mediation of this effect of EOCN.

Action Potentials↗

Cardiovascular effects of the essential oil of Mentha x villosa in DOCA-salt-hypertensive rats.

The present study investigated the effects of chronic treatment with deoxycorticosterone-acetate (DOCA)-salt on cardiovascular responses to intravenous (i.v.) injection of the essential oil of Mentha x villosa (EOMV) in conscious rats. In both DOCA-salt-hypertensive and uninephrectomized control, conscious rats, i.v. bolus injections of EOMV (1 to 20 mg/kg body wt.) decreased mean aortic pressure (MAP) and heart rate (HR) in a dose-dependent manner. Treatment with DOCA-salt significantly enhanced EOMV-induced decreases in MAP, without affecting bradycardia. Likewise, both maximal percent and absolute decreases in MAP elicited by i.v. injection of the ganglion blocker, hexamethonium (30 mg/kg body wt.), were significantly greater in DOCA-salt-hypertensive than in control rats. In DOCA-salt-hypertensive rats, i.v. pretreatment with hexamethonium (30 mg/kg body wt.) reduced the bradycardia elicited by EOMV (1 to 20 mg/kg body wt.) without affecting the enhancement of EOMV-induced hypotension. These results show that i.v. treatment with EOMV decreases blood pressure in conscious DOCA-salt-hypertensive rats dose-dependently, and that this action is enhanced when compared with uninephrectomized controls. This enhancement could be related mainly to an increase in EOMV-induced vascular smooth muscle relaxation, rather than to enhanced sympathetic nervous system activity in this hypertensive model.

Animals↗

Cardiovascular effects of the essential oil of Mentha x villosa and its main constituent, piperitenone oxide, in normotensive anaesthetised rats: role of the autonomic nervous system.

Cardiovascular effects of intravenous (i. v.) treatment with the essential oil of Mentha x villosa (EOMV) were investigated in pentobarbitone-anaesthetised rats. Additionally this study examines whether the major constituent of EOMV, piperitenone oxide (PO), is the active principle mediating EOMV-induced changes in mean aortic pressure (MAP) and heart rate (HR) and whether the autonomic nervous system is involved in the mediation of these cardiovascular effects. Two samples of EOMV have been tested: one contained 62.32% of PO (sample 1) and the other contained a higher percent (95.87%) of PO (sample 2). Intravenous injections of bolus doses (1 to 20 mg/kg) of both samples of EOMV elicited immediate and dose-dependent decreases in MAP and HR. These cardiovascular responses were also observed following i. v. injections of PO (1 to 20 mg/kg). However, maximal percent decreases in MAP and HR elicited by sample 2 of EOMV were significantly greater than those evoked by sample 1 of EOMV, while they were of the same order of magnitude as those elicited by PO. Pretreatment of rats with either bilateral vagotomy or i. v. methylatropine (1 mg/kg) did not modify significantly the hypotensive and bradycardic responses to EOMV. In contrast, pretreatment with i. v. hexamethonium (30 mg/kg) partially, but significantly, reduced the bradycardic effects of EOMV without affecting hypotension. The present study shows for the first time that i. v. treatment with EOMV in pentobarbitone-anaesthetised rats induces hypotensive and bradycardic effects, which appear mostly attributed to the actions of the major constituent of EOMV, PO. These cardiovascular effects appear to be independent since EOMV-induced bradycardia appears dependent upon the presence of an intact and functional sympathetic nerve drive to the heart, while EOMV-induced hypotension appears independent of the presence of an operational sympathetic nervous system. This suggests that hypotensive activity of EOMV may result from its vasodilatory effects directly upon vascular smooth muscle.

Animals↗

Effects of long-term pretreatment with isoproterenol on inotropic responsiveness to alpha-adrenoceptor stimulation: study in isolated perfused rat hearts.

The effects of chronic pretreatment with isoproterenol (5 mg kg(-1)) daily for 10 days on cardiac alpha-adrenergic responsiveness in Langendorff heart preparations were investigated. Isoproterenol pretreatment caused cardiac hypertrophy (29%) as shown by a significant increase in the ratio of ventricular dry weight to body weight. In preparations from isoproterenol-pretreated rats, both maximum increases in left ventricular systolic pressure and heart rate elicited by isoproterenol (10(-12) to 10(-4) M) were significantly reduced (the isoproterenol concentration producing 50% of the maximum positive inotropic and chronotropic responses was enhanced almost 32- and 4-fold, respectively), while the positive inotropic response to phenylephrine (10(-12) to 10(-4) M) was significantly enhanced (the phenylephrine concentration producing 50% of the maximum positive inotropic effect was reduced almost 100-fold), compared with saline-pretreated rats. In preparations from both groups, phenylephrine infusion induced non-significant changes in heart rate and its positive inotropic response was reduced in the presence of propranolol (10(-7) M) in the perfusion medium. Even under beta-adrenoceptor blockade, the curve for the phenylephrine-induced positive inotropic effect remained shifted upward after isoproterenol pretreatment. Chronic isoproterenol pretreatment induces the expected cardiac beta-adrenoceptor desensitization while simultaneously enhancing the positive inotropic responsiveness to phenylephrine in Langendorff heart preparations. These findings support the hypothesis that cardiac alpha1-adrenoceptor stimulation may contribute to the maintenance of myocardial function under conditions in which beta-adrenoceptor function is compromised.

Adrenergic alpha-Agonists↗

Influence of a multideficient diet from northeastern Brazil on resting blood pressure and baroreflex sensitivity in conscious, freely moving rats.

The "regional basic diet" or RBD is a multideficient diet (providing 8% protein) which is known to produce dietary deficiencies in some populations in northeastern Brazil. The present study investigated the effects of RBD-induced malnutrition on resting blood pressure and baroreflex sensitivity in conscious rats. Malnourished rats were obtained by feeding dams the RBD during mating and pregnancy (RBD-1 group) or during nursing and a 10-day period after weaning (RBD-2 group). At 90 days of age, only RBD-2 rats weighed significantly (P<0.001) less than control rats born to dams fed a standard commercial diet (23% protein) during pregnancy and nursing. Baseline mean arterial pressure and heart rate of both RBD-1 and RBD-2 rats were comparable to those of controls. The slopes for both reflex bradycardia and tachycardia (bpm/mmHg) induced by intravenous phenylephrine and sodium nitroprusside, respectively, were unchanged in either RBD-1 (-2.08 +/- 0.11 and -3.10 +/- 0.43, respectively) or RBD-2 (-2.32 +/- 0.30 and -3.73 +/- 0.53, respectively) rats, when compared to controls (-2.09 +/- 0.10 and -3.17 +/- 0.33, respectively). This study shows that, after a prolonged period of nutritional recovery, the patterns of resting blood pressure and baroreflex sensitivity of both pre- and postnatally malnourished rats were similar to those of controls. The decreased body weight and the tendency to increased reflex tachycardia in RBD-2 rats may suggest that this type of maternal malnutrition during lactation is more critical than during pregnancy.

Animals↗

Central bromocriptine-induced tachycardia is reversed to bradycardia in conscious, deoxycorticosterone acetate-salt hypertensive rats.

A central dopaminergic origin has been demonstrated for the bromocriptine-induced tachycardia in conscious, normotensive rats. The present study investigated the effect of bromocriptine on heart rate and the principal site of action of this agonist in conscious, deoxycorticosterone acetate-salt hypertensive rats, in which altered central dopaminergic activity has been previously reported. Intravenous administration of bromocriptine (150 microg/kg) increased heart rate (49+/-5 beats/min.) in uninephrectomized control rats, while it induced a significant bradycardia (50+/-6 beats/min.) in deoxycorticosterone acetate-salt hypertensive rats. In the latter animals, intravenous (500 microg/kg) or intrathecal (40 microg/rat at T9-T10) pretreatment with domperidone, a selective dopamine D2 receptor antagonist that does not cross the blood-brain barrier, reduced partially, but significantly, the bradycardiac responses to bromocriptine (reduction of about 44% and 48% of the maximal effect, respectively). In contrast, the bromocriptine-induced bradycardia was fully abolished by intravenous pretreatment with metoclopramide (300 microg/kg), a dopamine D2 receptor antagonist that crosses the blood-brain barrier, or by combined pretreatment with intravenous and intrathecal domperidone. These results indicate that, in deoxycorticosterone acetate-salt hypertensive rats, bromocriptine decreases rather than increases heart rate, an effect that is mediated partly through a peripheral D2 dopaminergic mechanism and partly through stimulation of spinal dopamine D2 receptors. They further support the concept that, in normotensive, conscious rats, the central tachycardia of bromocriptine appears to predominate and to mask the bradycardia of this agonist at both peripheral and spinal dopamine D2 receptors.

Animals↗

Blunted pressor responsiveness to intravenous quinpirole in conscious, chronic spinal cord-transected rats: peripheral vs. spinal mechanisms.

Intravenous quinpirole (1 mg/kg) in conscious rats with chronic spinal cord transection (at T5-T7) induced an initial pressor effect, which was significantly reduced in both magnitude and duration compared with that in sham-operated rats, which was then followed by a long-lasting depressor effect. To distinguish the spinal and/or peripheral origin of this phenomenon, conscious, spinal cord-transected rats were also pretreated with either intravenous (0. 5 mg/kg), intrathecal (40 microg/kg) or combined intravenous and intrathecal domperidone, a dopamine D(2) receptor antagonist that does not cross the blood-brain barrier. Intravenous pretreatment with domperidone enhanced, but did not completely restore, the pressor effect of quinpirole, and had no effect upon the depressor component. However, both the depressor component and the reduction of the pressor effect induced by spinal section were fully abolished by intrathecal or combined intrathecal and intravenous domperidone. Quinpirole-induced changes in mean aortic pressure were also fully abolished by intravenous pretreatment with metoclopramide (5 mg/kg). Neither the pressor nor the bradycardiac response to intravenous phenylephrine differed between sham-operated and spinal rats. These results suggest that the blunted pressor response to quinpirole after spinal cord transection is related to an enhanced spinal dopamine D(2) receptor-mediated depressor effect rather than to hypersensitivity of peripheral dopamine D(2) receptors or vascular hyporesponsiveness to alpha(1)-adrenoceptor stimulation. Thus, in conscious intact rats, the prominent central pressor effect of quinpirole seems to oppose, not only a peripheral sympathoinhibitory depressor effect, as previously thought, but also a spinal depressor effect.

Animals↗

Essential oil of Croton nepetaefolius decreases blood pressure through an action upon vascular smooth muscle: studies in DOCA-salt hypertensive rats.

Experiments tested the hypothesis that hypotensive effects of intravenous (i.v.) treatment with the essential oil of Croton nepetaefolius (EOCN) result from its vasodilatory effects directly upon vascular smooth muscle. In both deoxycorticosterone-acetate (DOCA)-salt hypertensive and uninephrectomised control, conscious rats, i.v. bolus injections of EOCN (1 to 50 mg/kg) decreased mean aortic pressure (MAP) and heart rate (HR) in a dose-related manner. Treatment with DOCA-salt significantly enhanced EOCN-induced decreases in MAP without affecting bradycardia. Likewise, both maximal percent and absolute decreases in MAP elicited by i.v. hexamethonium (30 mg/kg), a ganglion blocker, were significantly greater in DOCA-salt hypertensive than in control rats. In DOCA-salt hypertensive rats, i.v. pretreatment with hexamethonium (30 mg/kg) reduced the bradycardia elicited by EOCN (50 mg/kg) without affecting the enhancement of EOCN-induced hypotension. In isolated thoracic aorta preparations from DOCA-salt hypertensive rats, EOCN (1-300 micrograms/ml) induced a concentration-dependent reduction of phenylephrine-induced contraction. Arteries from DOCA rats showed increased sensitivity to EOCN, as evidenced by the significant decrease in the IC50 for EOCN-induced reduction of phenylephrine-induced contraction (16.4 +/- 3.6 vs. 112.9 +/- 23.4 micrograms/ml in uninephrectomized controls). These results show that i.v. treatment with EOCN dose-dependently decreases blood pressure in conscious DOCA-salt hypertensive rats, and this action is enhanced when compared with uninephrectomized controls. This enhancement appears to be related mainly to an increase in EOCN-induced vascular smooth muscle relaxation rather than to enhanced sympathetic nervous system activity in this hypertensive model. Thus, the hypothesis that EOCN may be a direct vasorelaxant agent is supported by the results of the present study.

Animals↗

Effects of long-term pretreatment with isoproterenol on bromocriptine-induced tachycardia in conscious rats.

It has been shown that bromocriptine-induced tachycardia, which persisted after adrenalectomy, is (i) mediated by central dopamine D2 receptor activation and (ii) reduced by 5-day isoproterenol pretreatment, supporting therefore the hypothesis that this effect is dependent on sympathetic outflow to the heart. This study was conducted to examine whether prolonged pretreatment with isoproterenol could abolish bromocriptine-induced tachycardia in conscious rats. Isoproterenol pretreatment for 15 days caused cardiac hypertrophy without affecting baseline blood pressure and heart rate. In control rats, intravenous bromocriptine (150 microg/kg) induced significant hypotension and tachycardia. Bromocriptine-induced hypotension was unaffected by isoproterenol pretreatment, while tachycardia was reversed to significant bradycardia, an effect that was partly reduced by i.v. domperidone (0.5 mg/kg). Neither cardiac vagal nor sympathetic tone was altered by isoproterenol pretreatment. In isolated perfused heart preparations from isoproterenol-pretreated rats, the isoproterenol-induced maximal increase in left ventricular systolic pressure was significantly reduced, compared with saline-pretreated rats (the EC50 of the isoproterenol-induced increase in left ventricular systolic pressure was enhanced approximately 22-fold). These results show that 15-day isoproterenol pretreatment not only abolished but reversed bromocriptine-induced tachycardia to bradycardia, an effect that is mainly related to further cardiac beta-adrenoceptor desensitization rather than to impairment of autonomic regulation of the heart. They suggest that, in normal conscious rats, the central tachycardia of bromocriptine appears to predominate and to mask the bradycardia of this agonist at peripheral dopamine D2 receptors.

Adrenergic beta-Agonists↗

Cardiovascular effects of the essential oil of Croton nepetaefolius in rats: role of the autonomic nervous system.

Cardiovascular effects of intravenous (i.v.) treatment with the essential oil of Croton nepetaefolius (EOCN) were investigated in rats. Additionally, this study examined the importance of the autonomic nervous system in mediation of the EOCN-induced changes in mean aortic pressure (MAP) and heart rate (HR). In both pentobarbitone-anaesthetised and conscious rats, i.v. bolus injections of EOCN (1 to 50 mg/kg) elicited dose-dependent decreases in MAP and HR. Both decreases were of the same order of magnitude or duration, irrespective of whether the animal was under general anaesthesia. Pretreatment of anaesthetised rats with bilateral vagotomy reduced the magnitude of EOCN-induced bradycardia without affecting hypotension. Likewise, i.v. pretreatment of conscious rats with either methylatropine (1 mg/kg) or hexamethonium (30 mg/kg) significantly decreased the bradycardic effects of EOCN by the same order of magnitude. Neither compound influenced the hypotensive effects elicited by EOCN. This is the first physiological evidence that i.v. treatment with EOCN in either anaesthetised or conscious rats elicits hypotension and bradycardia. EOCN-induced bradycardia appears dependent upon the presence of an intact and functional parasympathetic nerve drive to the heart. However, EOCN-induced hypotension appears independent of the presence of an operational sympathetic nervous system. This suggests that EOCN may be a direct vasorelaxant agent.

Animals↗

Cardiovascular responses to intrathecal dopamine receptor agonists in conscious DOCA-salt hypertensive rats.

Previous studies have demonstrated that in conscious deoxycorticosterone acetate (DOCA)-salt hypertensive rats, the hypotensive action of intravenous (i.v.) bromocriptine, a selective dopamine D2 receptor agonist, was mediated partly by peripheral and partly by spinal dopamine D2 receptor stimulation, and that this effect was greater and longer-lasting than that in uninephrectomized control rats. To determine whether this amplification results partly from a putative spinal hypersensitivity phenomenon, cardiovascular responses to intrathecal (i.t.) administration of apomorphine and quinpirole were studied in conscious, 4-week DOCA-salt hypertensive rats and compared with those in uninephrectomized control rats. In both groups, upper thoracic (T2-T4) i.t. injections of apomorphine (9.1, 45.5 and 91.1 microg/rat) induced immediate and dose-dependent decreases in mean aortic pressure (MAP) and heart rate (HR), while i.t. quinpirole (38.4 microg/rat) induced only bradycardia. Neither magnitude nor duration of these responses was enhanced in DOCA-salt hypertensive rats when compared to control rats. In DOCA-salt hypertensive rats, apomorphine-induced hypotension and bradycardia remained unaffected by i.v. (500 microg/kg) pretreatment with domperidone, a selective dopamine D2 receptor antagonist that does not cross the blood-brain barrier. However, i.t. (40 microg/rat at T2-T4) pretreatment with domperidone significantly reduced apomorphine-induced hypotension, but fully suppressed bradycardia elicited by either apomorphine or quinpirole. These results demonstrated that in conscious DOCA-salt hypertensive rats, intrathecally-injected apomorphine or quinpirole decreased MAP and/or HR through a spinal D2 dopaminergic mechanism, as previously demonstrated in normotensive intact rats. Since both magnitude and duration of these responses were unchanged with respect to uninephrectomized control rats, enhancement of the hypotensive effect of intravenously-administered bromocriptine in DOCA-salt hypertensive rats does not appear to involve spinal dopamine D2 receptors.

Analysis of Variance↗

Involvement of spinal dopamine receptors in mediation of the hypotensive and bradycardic effects of systemic quinpirole in anaesthetised rats.

This study examined the involvement of spinal dopamine D2 receptors in the cardiovascular effects induced by intravenous administration of the selective dopamine D2 receptor agonist quinpirole, as has been previously reported for the hypotensive action of systemic bromocriptine. In normotensive pentobartitone-anaesthetised rats, intravenous injection of quinpirole (25 to 1000 microg/kg) decreased mean aortic pressure and heart rate in a dose-related manner. The intravenous (0.5 mg/kg) or intrathecal (40 microg/rat at T9-T10) pretreatment with domperidone, a dopamine D2 receptor antagonist that does not cross the blood-brain barrier, significantly reduced the maximal hypotensive and bradycardic responses to intravenous quinpirole (1000 microg/kg). In contrast, the latter effects were fully abolished either by intravenous metoclopramide (5 mg/kg) or combined pretreatment with intravenous and intrathecal domperidone. In addition, when injected intrathecally at the T9-T10 level of the spinal cord, quinpirole (7.7 to 61.4 microg/rat) also produced dose-dependent depressor and bradycardic effects which could be blocked by intrathecal, but not intravenous, domperidone pretreatment. This suggests that, in anaesthetised normotensive rats, the hypotensive and bradycardic responses to intravenous quinpirole are fully mediated by dopamine D2 receptors, some of which are located in the peripheral circulation and some of which are located within the spinal cord. The latter finding is novel, suggesting that partial spinal mediation may not be peculiar to bromocriptine, as was previously thought. Rather, partial spinal mediation may be common to most dopamine D2 receptor agonists.

Animals↗

Hypotensive action of bromocriptine in the DOCA-salt hypertensive rat: contribution of spinal dopamine receptors.

To assess the role of spinal dopamine receptors in mediation of hypotension induced by systemic administration of the dopamine D2 receptor agonist, bromocriptine, conscious deoxycorticosterone acetate (DOCA)-salt hypertensive rats were pretreated with either intravenous (i.v.; 500 micrograms/kg) or intrathecal (i.t.; 40 micrograms/rat at T9-T10) domperidone, a selective dopamine D2 receptor antagonist that does not cross the blood-brain barrier. In DOCA-salt hypertensive rats, i.v. administration of a sub-maximal dose of bromocriptine (150 micrograms/kg) induced a significant decrease in mean aortic pressure (MAP) which was greater and longer lasting than that in uninephrectomized control rats. Intravenous or i.t. pretreatment with domperidone reduced partially, but significantly, the hypotensive effect of bromocriptine (reduction of about 57% and 45% of the maximal effect, respectively). The remaining responses observed during the 60 min postinjection period were still statistically significant as compared with vehicle injection. In contrast, the bromocriptine-induced hypotension was fully abolished by i.v. pretreatment with metoclopramide (300 micrograms/kg), a dopamine D2 receptor antagonist that crosses the blood-brain barrier, or by combined pretreatment with i.v. and i.t. domperidone. These results suggest that, in DOCA-salt hypertensive rats, the hypotension induced by i.v. bromocriptine is mediated partly through a peripheral D2 dopaminergic mechanism and partly through stimulation of spinal dopamine D2 receptors, has been demonstrated in conscious normotensive rats.

Animals↗

Bromocriptine-induced tachycardia in conscious rats: blunted response following isoproterenol pretreatment for 5 days.

Previous studies have shown that tachycardia induced by intravenous injection of bromocriptine, which persisted after adrenalectomy, was mediated by central dopamine D2 receptor stimulation. Such stimulation could activate central sympathetic outflow to the heart. To test this hypothesis, we investigated whether pretreatment with isoproterenol, known to induce cardiac beta-adrenoceptor desensitization, could reduce bromocriptine-induced tachycardia. A 5 day pretreatment with isoproterenol (5 mg/kg/day) induced a 21% increase in the ratio of ventricular dry weight to body weight, compared with saline-pretreated rats. In isolated perfused heart preparations from isoproterenol-pretreated rats, the isoproterenol-induced increase in left ventricular systolic pressure and heart rate was significantly reduced, compared with saline-pretreated rats (the isoproterenol concentration producing 50% of the maximal positive inotropic and chronotropic responses was increased approximately 5- and 4-fold, respectively). In conscious control rats, intravenous injection of bromocriptine (50, 150 and 250 micrograms/kg) decreased mean aortic pressure and increased heart rate in a dose-related manner. Pretreatment with isoproterenol for 5 days reduced bromocriptine-induced tachycardia without affecting hypotension. Cardiac autonomic tone remained of the same order of magnitude irrespective of whether the animal was pretreated with isoproterenol. These results indicate that isoproterenol pretreatment reduces bromocriptine-induced tachycardia mainly through desensitization of cardiac beta-adrenoceptors rather than via an impairment of autonomic regulation of the heart. This supports the hypothesis that bromocriptine-induced activation of central dopamine D2 receptors increases heart rate via activation of central sympathetic outflow to the heart.

Adrenergic beta-Agonists↗

Na+/H+ exchange and osmotic shrinkage in isolated trout hepatocytes

The ability of rainbow trout liver cells to regulate their intracellular pH (pHi) was studied using two methods on hepatocytes isolated by collagenase digestion: (i) by monitoring pHi with the fluorescent dye BCECF-AM, and (ii) by measuring the amiloride-sensitive uptake of 22Na, which represents Na+/H+ exchange. In low-Na+ medium (&frac34;16mmoll-1), Na+ uptake was reduced by approximately 70% in the presence of amiloride derivatives (DMA or MPA, 10(-4)moll-1). Changing separately either the extracellular pH (pHe) or the intracellular pH (pHi, clamped by treating the cells with nigericin in the presence of 140mmoll-1 K+) between 6 and 8 induced an increase in the rate of Na+ uptake when pHe was raised or when pHi was reduced. When transferred to hypertonic medium, hepatocytes shrank to nearly 72% of their initial volume, and thereafter a slow and partial regulatory volume increase phase was observed, with an increase in the amiloride-sensitive rate of Na+ uptake and an increase in intracellular pH. As DIDS-sensitive Cl- uptake was concomitantly enhanced, it is suggested that hypertonic stress activates Na+/H+ and Cl-/HCO3- exchange.

Journal Article↗

Central dopaminergic origin of bromocriptine induced tachycardia in normotensive rats.

OBJECTIVES: This study was undertaken to investigate the mechanism of the tachycardic effect of bromocriptine, a specific dopamine D-2 receptor agonist, which is not abolished, as previously reported, by intravenous domperidone, a selective dopamine D-2 antagonist unable to cross the blood brain barrier. Two hypotheses were tested: (1) that the increase in heart rate after intravenous treatment with bromocriptine could be related to central dopamine receptor stimulation and (2) that it could be induced by a release of adrenaline from the adrenal medulla. METHODS: Changes in mean aortic pressure and heart rate, induced by treatment with 150 micrograms.kg-1 bromocriptine intravenously, were measured in conscious or anaesthetised normal or adrenalectomised rats submitted to various pretreatments. RESULTS: In conscious intact rats, intravenous bromocriptine decreased mean aortic pressure (-11 (SEM1) mm Hg) and increased heart rate (62(12)) beats.min-1). Both effects were prevented by intravenous pretreatment (0.3 mg.kg-1) with dopamine D-2 receptor antagonists able to cross the blood brain barrier, such as haloperidol, sulpiride, and metoclopramide. In anaesthetised rats, domperidone (50 and 20 micrograms.kg-1) given via a lateral cerebral ventricle abolished the bromocriptine induced tachycardia without affecting the hypotensive response. Both effects were unchanged after bilateral adrenalectomy but were completely abolished by intravenous haloperidol pretreatment (0.3 mg.kg-1) in conscious adrenalectomised rats. CONCLUSIONS: These results suggest that in anaesthetised and conscious normotensive rats, the bromocriptine induced tachycardia is not related to a release of adrenaline from the adrenal medulla but could be elicited by central dopamine D-2 receptor stimulation through a possible increase in cardiac sympathetic tone.

Adrenalectomy↗

Cardiovascular responses to intrathecal dopamine receptor agonists after spinal transection in conscious rats.

OBJECTIVE: The cardiovascular responses to transient intrathecal administration of dopamine agonists were studied daily in chronically prepared rats that had been spinally transected or were sham operated. The goals were (1) to determine the group differences in evoked heart rate and arterial pressure responses and (2) to determine, within the transected group, whether or not the long term responses could be dissociated. The hypothesis tested is that cord transection releases a tonic inhibition of cardiovascular responsiveness independently of the mechanism of receptor hypersensitivity. METHODS: Changes in mean aortic blood pressure and heart rate induced by intrathecal administration of the mixed D1/D2 dopamine receptor agonist apomorphine (150 nmol per rat) were measured in conscious rats during a 10 d experimental period following spinal transection. RESULTS: Complete spinal transection did not affect aortic pressure but increased basal heart rate values by about 33% with respect to normal rats (p < 0.001). When apomorphine was injected caudally to the section (at T9-T10) but not rostrally (at T2-T4), it induced a 50% greater and an 800% more long lasting decrease in mean aortic pressure and a 230% greater and 70% more long lasting decrease in heart rate in spinal than in sham operated rats. These increases in cardiovascular responses were corroborated by a leftward shift of the apomorphine dose-response curves. They were also found after intrathecal administration of highly selective D1 and D2 receptor agonists fenoldopam (50 nmol per rat) and quinpirole (150 nmol per rat), and were specifically blocked by intrathecal haloperidol (27 nmol per rat), a non-selective dopamine antagonist. CONCLUSIONS: Complete spinal transection induces different increases in hypotensive and bradycardic responses to the stimulation of caudally located spinal dopamine receptors which could be due to the destruction of a tonically inhibiting spinal system rather than to hypersensitivity of the dopamine receptors.

Animals↗