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Geoffrey A. Head - One of the best experts on this subject based on the ideXlab platform.
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Upper: Average mid frequency (MF, 0.25–0.6 Hz) MAP power (mmHg)2, MF HR power (bpm)2, Middle: Coherence (units), baroreflex gain, (gain, bpm/mmHg), Lower: low frequency (LF, 0.05–0.25 Hz) and high frequency (HF, 0.6–1.0 Hz) MAP power (mmHg)2 from cro
2016Co-Authors: Kyungjoon Lim, Kristy L. Jackson, Sandra L. Burke, Geoffrey A. HeadAbstract:Measurements are 2 weeks after vehicle (V, open bars), perindopril (P, hatched bars) and Rilmenidine (R, crosshatched bars) in SHR (n = 7–9 per group). Values are mean ± SEM. Effect of perindopril or Rilmenidine compared with vehicle *, P
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actions of Rilmenidine on neurogenic hypertension in bph 2j genetically hypertensive mice
Journal of Hypertension, 2014Co-Authors: Kristy L. Jackson, Pamela J. Davern, Kesia Palmarigo, Thuphuc Nguyenhuu, Geoffrey A. HeadAbstract:Objective: BPH/2J hypertensive mice have an exaggeratedsympathetic contribution to blood pressure (BP). Premotorsympathetic neurons within the rostroventrolateral medulla(RVLM) are a major source of sympathetic vasomotor toneand major site of action of the centrally actingsympatholytic agent, Rilmenidine. The relativecardiovascular effect of Rilmenidine in BPH/2J versusnormotensive BPN/3J mice was used as an indicator of theinvolvement of the RVLM in the sympathetic contributionto hypertension in BPH/2J mice.Methods: BPH/2J and BPN/3J mice were pre-implantedwith telemetry devices to measure BP in consciousunrestrained mice. Rilmenidine was administered acutely(n¼7–9/group), orally for 14 days, at a wide range ofdoses (n¼5/group), and also infusedintracerebroventricularly for 7 days (n¼6/group).Results: Acute intraperitoneal Rilmenidine induced greaterdepressor and bradycardic responses in BPH/2J than BPN/3Jmice (P
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Actions of Rilmenidine on neurogenic hypertension in BPH/2J genetically hypertensive mice
Journal of hypertension, 2014Co-Authors: Kristy L. Jackson, Kesia Palma-rigo, Thu-phuc Nguyen-huu, Pamela J. Davern, Geoffrey A. HeadAbstract:Objective: BPH/2J hypertensive mice have an exaggeratedsympathetic contribution to blood pressure (BP). Premotorsympathetic neurons within the rostroventrolateral medulla(RVLM) are a major source of sympathetic vasomotor toneand major site of action of the centrally actingsympatholytic agent, Rilmenidine. The relativecardiovascular effect of Rilmenidine in BPH/2J versusnormotensive BPN/3J mice was used as an indicator of theinvolvement of the RVLM in the sympathetic contributionto hypertension in BPH/2J mice.Methods: BPH/2J and BPN/3J mice were pre-implantedwith telemetry devices to measure BP in consciousunrestrained mice. Rilmenidine was administered acutely(n¼7–9/group), orally for 14 days, at a wide range ofdoses (n¼5/group), and also infusedintracerebroventricularly for 7 days (n¼6/group).Results: Acute intraperitoneal Rilmenidine induced greaterdepressor and bradycardic responses in BPH/2J than BPN/3Jmice (P
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Contribution of imidazoline receptors and α2-adrenoceptors in the rostral ventrolateral medulla to sympathetic baroreflex inhibition by systemic Rilmenidine
Journal of hypertension, 2007Co-Authors: Candy K. S. Chan, Sandra L. Burke, Geoffrey A. HeadAbstract:OBJECTIVES To determine whether the hypotensive and sympathetic baroreflex inhibition by Rilmenidine administered systemically are mediated via imidazoline receptors in the rostral ventrolateral medulla (RVLM). METHODS Initial dose-response curves to Rilmenidine were determined in urethane anaesthetized rabbits. Effects of a single intravenous dose of Rilmenidine (445 microg/kg) on the renal sympathetic nerve activity (RSNA) baroreflex were examined before and after microinjection into the RVLM of the mixed imidazoline/alpha2-adrenoceptor antagonist idazoxan and the alpha2-adrenoceptor antagonist 2-methoxyidazoxan (2-MI). RESULTS Intravenous administration of Rilmenidine lowered mean arterial pressure and RSNA, inhibited the RSNA baroreflex range by 33% and shifted the baroreflex curve to the left. Idazoxan injected into the RVLM reversed the hypotension and completely restored the baroreflex curve at doses that did not affect the hypotension produced by the selective alpha2-adrenoceptor agonist alpha-methylnoradrenaline. The alpha2-adrenoceptor antagonist, 2-MI also reversed the Rilmenidine sympatho-inhibition suggesting that alpha2-adrenoceptors are activated as well. CONCLUSIONS The results of the present study show that the hypotensive and sympatho-inhibitory actions of systemic Rilmenidine are primarily mediated via imidazoline receptors in the RVLM. However, alpha2-adrenoceptors are also involved, probably as a direct result of the imidazoline receptor action.
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Sympathetic Responses to Stress and Rilmenidine in 2K1C Rabbits. Evidence of Enhanced Nonvascular Effector Mechanism
Hypertension (Dallas Tex. : 1979), 2004Co-Authors: Geoffrey A. Head, Sandra L. BurkeAbstract:We determined whether the sympathetic excitatory responses to environmental stressors and the sympathoinhibitory responses to Rilmenidine are altered by renovascular hypertension. Rabbits were made hypertensive with a clip on the right renal artery, and a left renal nerve recording electrode was implanted. After 3 or 6 weeks, the animals were given air-jet stress and loud noise stress before and after intravenous Rilmenidine. Three and 6 weeks after renal clipping, mean arterial pressure was 28% and 36% greater than preclip values. Air-jet stress elicited a marked increase in renal sympathetic nerve activity, mean arterial pressure, and heart rate. Renal sympathetic nerve activity responses were much greater in hypertensive rabbits, but the pressor responses were similar to those observed in normotensive animals. Acute administration of Rilmenidine decreased blood pressure more in hypertensive animals but with a much lesser inhibition of sympathetic activity. Rilmenidine markedly reduced increased sympathetic activity during air-jet stress in 3-week clipped rabbits but to a lesser extent in the other groups. These studies show that while sympathetic responses to stress were markedly enhanced in renal clip hypertensive rabbits, they did not result in greater pressor responses, thus suggesting that vascular neuroeffector mechanisms were not altered. By contrast, the increased effects of Rilmenidine suggest a much greater contribution to the hypertension by the sympathetic nervous system, but one that is caused by an enhanced “nonvascular” neuroeffector mechanism. As such, sympathoinhibitory agents such as Rilmenidine are very suitable and very effective agents for the treatment of renovascular hypertension.
Sandra L. Burke - One of the best experts on this subject based on the ideXlab platform.
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Upper: Average mid frequency (MF, 0.25–0.6 Hz) MAP power (mmHg)2, MF HR power (bpm)2, Middle: Coherence (units), baroreflex gain, (gain, bpm/mmHg), Lower: low frequency (LF, 0.05–0.25 Hz) and high frequency (HF, 0.6–1.0 Hz) MAP power (mmHg)2 from cro
2016Co-Authors: Kyungjoon Lim, Kristy L. Jackson, Sandra L. Burke, Geoffrey A. HeadAbstract:Measurements are 2 weeks after vehicle (V, open bars), perindopril (P, hatched bars) and Rilmenidine (R, crosshatched bars) in SHR (n = 7–9 per group). Values are mean ± SEM. Effect of perindopril or Rilmenidine compared with vehicle *, P
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Contribution of imidazoline receptors and α2-adrenoceptors in the rostral ventrolateral medulla to sympathetic baroreflex inhibition by systemic Rilmenidine
Journal of hypertension, 2007Co-Authors: Candy K. S. Chan, Sandra L. Burke, Geoffrey A. HeadAbstract:OBJECTIVES To determine whether the hypotensive and sympathetic baroreflex inhibition by Rilmenidine administered systemically are mediated via imidazoline receptors in the rostral ventrolateral medulla (RVLM). METHODS Initial dose-response curves to Rilmenidine were determined in urethane anaesthetized rabbits. Effects of a single intravenous dose of Rilmenidine (445 microg/kg) on the renal sympathetic nerve activity (RSNA) baroreflex were examined before and after microinjection into the RVLM of the mixed imidazoline/alpha2-adrenoceptor antagonist idazoxan and the alpha2-adrenoceptor antagonist 2-methoxyidazoxan (2-MI). RESULTS Intravenous administration of Rilmenidine lowered mean arterial pressure and RSNA, inhibited the RSNA baroreflex range by 33% and shifted the baroreflex curve to the left. Idazoxan injected into the RVLM reversed the hypotension and completely restored the baroreflex curve at doses that did not affect the hypotension produced by the selective alpha2-adrenoceptor agonist alpha-methylnoradrenaline. The alpha2-adrenoceptor antagonist, 2-MI also reversed the Rilmenidine sympatho-inhibition suggesting that alpha2-adrenoceptors are activated as well. CONCLUSIONS The results of the present study show that the hypotensive and sympatho-inhibitory actions of systemic Rilmenidine are primarily mediated via imidazoline receptors in the RVLM. However, alpha2-adrenoceptors are also involved, probably as a direct result of the imidazoline receptor action.
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Sympathetic Responses to Stress and Rilmenidine in 2K1C Rabbits. Evidence of Enhanced Nonvascular Effector Mechanism
Hypertension (Dallas Tex. : 1979), 2004Co-Authors: Geoffrey A. Head, Sandra L. BurkeAbstract:We determined whether the sympathetic excitatory responses to environmental stressors and the sympathoinhibitory responses to Rilmenidine are altered by renovascular hypertension. Rabbits were made hypertensive with a clip on the right renal artery, and a left renal nerve recording electrode was implanted. After 3 or 6 weeks, the animals were given air-jet stress and loud noise stress before and after intravenous Rilmenidine. Three and 6 weeks after renal clipping, mean arterial pressure was 28% and 36% greater than preclip values. Air-jet stress elicited a marked increase in renal sympathetic nerve activity, mean arterial pressure, and heart rate. Renal sympathetic nerve activity responses were much greater in hypertensive rabbits, but the pressor responses were similar to those observed in normotensive animals. Acute administration of Rilmenidine decreased blood pressure more in hypertensive animals but with a much lesser inhibition of sympathetic activity. Rilmenidine markedly reduced increased sympathetic activity during air-jet stress in 3-week clipped rabbits but to a lesser extent in the other groups. These studies show that while sympathetic responses to stress were markedly enhanced in renal clip hypertensive rabbits, they did not result in greater pressor responses, thus suggesting that vascular neuroeffector mechanisms were not altered. By contrast, the increased effects of Rilmenidine suggest a much greater contribution to the hypertension by the sympathetic nervous system, but one that is caused by an enhanced “nonvascular” neuroeffector mechanism. As such, sympathoinhibitory agents such as Rilmenidine are very suitable and very effective agents for the treatment of renovascular hypertension.
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Relative importance of rostral ventrolateral medulla in sympathoinhibitory action of Rilmenidine in conscious and anesthetized rabbits.
Journal of cardiovascular pharmacology, 2001Co-Authors: Dmitry N. Mayorov, Sandra L. Burke, Geoffrey A. HeadAbstract:The pressor region of the rostral ventrolateral medulla (RVLM) is a critical site in the sympathoinhibitory action of imidazoline receptor agonists as shown by studies in anesthetized animals. The aim of this study was to compare the importance of the RVLM in mediating the inhibitory action of Rilmenidine on renal sympathetic nerve activity (RSNA) and arterial pressure in urethane-anesthetized rabbits (n = 11) and in conscious, chronically instrumented rabbits (n = 6). Bilateral microinjection of Rilmenidine (4 nmol in 100 nl) into the RVLM caused a greater decrease in resting arterial pressure in anesthetized animals (-19 mm Hg) than in conscious animals (-8 mm Hg). By contrast, the decrease in resting RSNA evoked by Rilmenidine was similar in conscious (-27%) and anesthetized (-36%) rabbits. Furthermore, Rilmenidine microinjection into the RVLM was equally effective in inhibiting the RSNA baroreflex in both groups of animals. The upper plateau of the RSNA baroreflex decreased by 37% and 42%, and gain decreased by 41% and 44% after Rilmenidine treatments in conscious and anesthetized rabbits, respectively. We conclude that the RVLM plays an equally important role in the inhibitory action of Rilmenidine on RSNA in conscious and anesthetized rabbits either at rest or during baroreflex responses. A relatively moderate effect of Rilmenidine on arterial pressure in conscious, chronically instrumented rabbits may relate to a lower level of sympathetic drive compared with anesthetized animals.
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i1 imidazoline receptors in cardiovascular regulation the place of Rilmenidine
American Journal of Hypertension, 2000Co-Authors: Geoffrey A. Head, Sandra L. BurkeAbstract:From the very earliest suggestion of a distinction between imidazoline receptors and a2adrenoceptors, there has been much debate as to their contribution to the antihypertensive actions of clonidine-like agents. However, with the development of drugs such as Rilmenidine that are more selective for I1 imidazoline receptors, their role and also their close relationship with a2adrenoceptors has become clearer. We have examined this question using a range of imidazoline and a2-adrenoceptor antagonists given centrally and peripherally to conscious rabbits. We found that second-generation agents such as Rilmenidine preferentially act via imidazoline receptors but that a2-adrenoceptors are important for the hypotension produced by the firstgeneration agents clonidine and a-methyldopa. In addition to the hypotension, Rilmenidine facilitates cardiac vagal baroreflexes and inhibits cardiac sympathetic baroreflexes and diminishes the increase in renal sympathetic activity produced by environmental stress. In other studies using anesthetized rabbits and direct measures of sympathetic nerve activity, we confirmed that the major site of sympathoinhibitory actions and sympathetic baroreflex effects of Rilmenidine is the rostral ventrolateral medulla. Our results also suggest that a2-adrenoceptors are activated as a consequence of imidazoline receptor activation by Rilmenidine. Thus, though imidazoline receptors appear to be the primary target of Rilmenidine, “downstream” a2-adrenoceptors within the brainstem are also involved and need to be considered in developing pharmacologic strategies for antihypertensive treatment involving imidazoline agents. Am J Hypertens 2000; 13:89S‐98S © 2000 American Journal of Hypertension, Ltd.
Paul M. Vanhoutte - One of the best experts on this subject based on the ideXlab platform.
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Rilmenidine activates postjunctional alpha1‐ and alpha2‐adrenoceptors in the canine saphenous vein
Fundamental & clinical pharmacology, 1996Co-Authors: Robert Marsault, Stefano Taddei, C. M. Boulanger, S Illiano, Paul M. VanhoutteAbstract:Experiments were performed to determine the subtypes of alpha-adrenoceptors involved in the contraction induced by Rilmenidine in isolated canine cutaneous veins. Rings of saphenous vein (without endothelium) were suspended for the recording of isometric force in physiological salt solution. All experiments were performed in the presence of propranolol (to antagonize beta-adrenoceptors), cocaine (to inhibit neuronal uptake) and hydrocortisone (to inhibit extraneuronal uptake). In the presence of rauwolscine (an alpha 2 -adrenergic blocker), Rilmenidine caused concentration-dependent contractions which were inhibited by prazosin (nonselective alpha 1 -antagonist) and by (+)niguldipine (selective alpha 1A -adrenergic antagonist), but not by (-)niguldipine. After treatment with phenoxybenzamine (to alkylate alpha 1 -adrenoceptors), Rilmenidine evoked contractions of the canine saphenous vein which were antagonized competitively by rauwolscine. The combination of rauwolscine and prazosin did not abolish contractions evoked by the highest concentrations of Rilmenidine. Although binding experiments using 3 H-idazoxan suggested the existence of a nonadrenergic binding site (around 20% of the total binding), contractile studies failed to demonstrate their involvement in the increases in tension evoked by Rilmenidine. These experiments suggest that the contractions evoked by Rilmenidine in isolated canine veins are mediated by both alpha 1A - and alpha 2 -adrenoceptors.
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Rilmenidine activates postjunctional alpha1 and alpha2 adrenoceptors in the canine saphenous vein
Fundamental & Clinical Pharmacology, 1996Co-Authors: Robert Marsault, Stefano Taddei, C. M. Boulanger, S Illiano, Paul M. VanhoutteAbstract:Experiments were performed to determine the subtypes of alpha-adrenoceptors involved in the contraction induced by Rilmenidine in isolated canine cutaneous veins. Rings of saphenous vein (without endothelium) were suspended for the recording of isometric force in physiological salt solution. All experiments were performed in the presence of propranolol (to antagonize beta-adrenoceptors), cocaine (to inhibit neuronal uptake) and hydrocortisone (to inhibit extraneuronal uptake). In the presence of rauwolscine (an alpha 2 -adrenergic blocker), Rilmenidine caused concentration-dependent contractions which were inhibited by prazosin (nonselective alpha 1 -antagonist) and by (+)niguldipine (selective alpha 1A -adrenergic antagonist), but not by (-)niguldipine. After treatment with phenoxybenzamine (to alkylate alpha 1 -adrenoceptors), Rilmenidine evoked contractions of the canine saphenous vein which were antagonized competitively by rauwolscine. The combination of rauwolscine and prazosin did not abolish contractions evoked by the highest concentrations of Rilmenidine. Although binding experiments using 3 H-idazoxan suggested the existence of a nonadrenergic binding site (around 20% of the total binding), contractile studies failed to demonstrate their involvement in the increases in tension evoked by Rilmenidine. These experiments suggest that the contractions evoked by Rilmenidine in isolated canine veins are mediated by both alpha 1A - and alpha 2 -adrenoceptors.
Robert Marsault - One of the best experts on this subject based on the ideXlab platform.
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Rilmenidine activates postjunctional alpha1‐ and alpha2‐adrenoceptors in the canine saphenous vein
Fundamental & clinical pharmacology, 1996Co-Authors: Robert Marsault, Stefano Taddei, C. M. Boulanger, S Illiano, Paul M. VanhoutteAbstract:Experiments were performed to determine the subtypes of alpha-adrenoceptors involved in the contraction induced by Rilmenidine in isolated canine cutaneous veins. Rings of saphenous vein (without endothelium) were suspended for the recording of isometric force in physiological salt solution. All experiments were performed in the presence of propranolol (to antagonize beta-adrenoceptors), cocaine (to inhibit neuronal uptake) and hydrocortisone (to inhibit extraneuronal uptake). In the presence of rauwolscine (an alpha 2 -adrenergic blocker), Rilmenidine caused concentration-dependent contractions which were inhibited by prazosin (nonselective alpha 1 -antagonist) and by (+)niguldipine (selective alpha 1A -adrenergic antagonist), but not by (-)niguldipine. After treatment with phenoxybenzamine (to alkylate alpha 1 -adrenoceptors), Rilmenidine evoked contractions of the canine saphenous vein which were antagonized competitively by rauwolscine. The combination of rauwolscine and prazosin did not abolish contractions evoked by the highest concentrations of Rilmenidine. Although binding experiments using 3 H-idazoxan suggested the existence of a nonadrenergic binding site (around 20% of the total binding), contractile studies failed to demonstrate their involvement in the increases in tension evoked by Rilmenidine. These experiments suggest that the contractions evoked by Rilmenidine in isolated canine veins are mediated by both alpha 1A - and alpha 2 -adrenoceptors.
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Rilmenidine activates postjunctional alpha1 and alpha2 adrenoceptors in the canine saphenous vein
Fundamental & Clinical Pharmacology, 1996Co-Authors: Robert Marsault, Stefano Taddei, C. M. Boulanger, S Illiano, Paul M. VanhoutteAbstract:Experiments were performed to determine the subtypes of alpha-adrenoceptors involved in the contraction induced by Rilmenidine in isolated canine cutaneous veins. Rings of saphenous vein (without endothelium) were suspended for the recording of isometric force in physiological salt solution. All experiments were performed in the presence of propranolol (to antagonize beta-adrenoceptors), cocaine (to inhibit neuronal uptake) and hydrocortisone (to inhibit extraneuronal uptake). In the presence of rauwolscine (an alpha 2 -adrenergic blocker), Rilmenidine caused concentration-dependent contractions which were inhibited by prazosin (nonselective alpha 1 -antagonist) and by (+)niguldipine (selective alpha 1A -adrenergic antagonist), but not by (-)niguldipine. After treatment with phenoxybenzamine (to alkylate alpha 1 -adrenoceptors), Rilmenidine evoked contractions of the canine saphenous vein which were antagonized competitively by rauwolscine. The combination of rauwolscine and prazosin did not abolish contractions evoked by the highest concentrations of Rilmenidine. Although binding experiments using 3 H-idazoxan suggested the existence of a nonadrenergic binding site (around 20% of the total binding), contractile studies failed to demonstrate their involvement in the increases in tension evoked by Rilmenidine. These experiments suggest that the contractions evoked by Rilmenidine in isolated canine veins are mediated by both alpha 1A - and alpha 2 -adrenoceptors.
P Pacaud - One of the best experts on this subject based on the ideXlab platform.
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Antagonism of alpha1-adrenoceptor agonist-induced responses by Rilmenidine in vascular smooth muscle.
European journal of pharmacology, 1998Co-Authors: C Cario-toumaniantz, G Loirand, P PacaudAbstract:The effect of the centrally acting antihypertensive agent, Rilmenidine, was examined on the contractile properties of isolated rat portal vein strips and on the free cytosolic [Ca2+] ([Ca2+]i) in isolated myocytes. Rilmenidine (1-30 microM) relaxed strips precontracted with noradrenaline. This effect was not inhibited by the alpha2-adrenoceptor antagonist, yohimbine, and was not mimicked by the alpha2-adrenoceptor agonist, 5-bromo-N-(4,5-dihydro-1H-imidazol-2-yl)-6-quinoxalinamine (UK 14,304). Rilmenidine dose dependently shifted to the right the concentration-response curves to noradrenaline and to phenylephrine but not that to carbachol. Rilmenidine alone (0.1-30 microM) caused a contraction which maximally corresponded to 18% of the maximal noradrenaline-induced contraction. This effect was not produced by UK 14,304, was not affected by yohimbine, but was inhibited by the alpha1-adrenoceptor antagonist, prazosin. In isolated myocytes, Rilmenidine reduced the noradrenaline-induced [Ca2+]i increase but alone, it produced a rise in [Ca2+]i, the peak amplitude of which averaged 15% of the noradrenaline-induced transient [Ca2+]i rise. It is concluded that Rilmenidine acts as a partial agonist of alpha1-adrenoceptors of vascular smooth muscle, causing relaxation of vessels precontracted by full agonists of alpha1-adrenoceptors.
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Antagonism of α1-adrenoceptor agonist-induced responses by Rilmenidine in vascular smooth muscle
European Journal of Pharmacology, 1998Co-Authors: C Cario-toumaniantz, G Loirand, P PacaudAbstract:Abstract The effect of the centrally acting antihypertensive agent, Rilmenidine, was examined on the contractile properties of isolated rat portal vein strips and on the free cytosolic [Ca2+] ([Ca2+]i) in isolated myocytes. Rilmenidine (1–30 μM) relaxed strips precontracted with noradrenaline. This effect was not inhibited by the α2-adrenoceptor antagonist, yohimbine, and was not mimicked by the α2-adrenoceptor agonist, 5-bromo-N-(4,5-dihydro-1H-imidazol-2-yl)-6-quinoxalinamine (UK 14,304). Rilmenidine dose dependently shifted to the right the concentration–response curves to noradrenaline and to phenylephrine but not that to carbachol. Rilmenidine alone (0.1–30 μM) caused a contraction which maximally corresponded to 18% of the maximal noradrenaline-induced contraction. This effect was not produced by UK 14,304, was not affected by yohimbine, but was inhibited by the α1-adrenoceptor antagonist, prazosin. In isolated myocytes, Rilmenidine reduced the noradrenaline-induced [Ca2+]i increase but alone, it produced a rise in [Ca2+]i, the peak amplitude of which averaged 15% of the noradrenaline-induced transient [Ca2+]i rise. It is concluded that Rilmenidine acts as a partial agonist of α1-adrenoceptors of vascular smooth muscle, causing relaxation of vessels precontracted by full agonists of α1-adrenoceptors.
