Experimental Studies on the Neurocardiovascular Effects of Urapidil

Gillis, Richard A.; Kellar, Kenneth J.; Quest, John A.; Namath, I J; Martino-Barrows, Andrea M.; Hill, K. J.; Gatti, Philip J.; Dretchen, Kenneth L.

doi:10.2165/00003495-198800356-00004

Cited by 38 publications

(8 citation statements)

References 13 publications

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“…Urapidii exerted the well known dose-dependent decrease in arterial blood pressure, which is attributed to blockade of peripheral vascular alpha-l-adrenoceptors (14,24,28,32,33) and to a stimulation of 5-HT-1A receptors in the brain (2,7,15). The reduction in afterload might have improved the systolic shortening of the ischemic myocardial area, as recently verified (12,16) in agreement with the original work of Frank (3).…”

Section: Reduction Of Afterloadsupporting

confidence: 68%

“…It is considered to lower blood pressure predominantly by blocking peripheral vascular alpha-l-adrenoceptors (14,24,28,32,33) and by a central action (7,14,20,24,28,33). In addition, there are reports on blockade of cardiac presynaptic alpha-2-adrenoceptors (25) and beta-l-receptors (5,19,24,25,29,33), as well as stimulation of the latter (21,33).…”

Section: Introductionmentioning

confidence: 99%

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Effect of urapidil on the performance of ischemic myocardium in anesthetized dogs

et al. 1990

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Urapidil (URA) is used to treat acute hypertension in patients with coronary artery disease, but the effect of URA on the performance of ischemic myocardium has not yet been investigated. The present study was intended to assess the function of ischemic myocardium following URA administration. In eight anesthetized (piritramide) open-chest dogs systolic contraction (dL) and end-diastolic length (edL) of myocardium supplied by the left descending (LAD) and circumflex (LCA) coronary arteries were measured by sonomicrometry simultaneously with aortic pressure (AoP), left ventricular end-diastolic pressure (LVedP), heart rate (HR), stroke volume (SV), and LAD-flow (QLAD). QLAD was reduced by LAD stenosis to about 50% of control, decreasing dLLAD by 55%. Concomitantly, edLLAD increased by about 9% and LVedP by 22%, whereas AoP decreased by 5%. Then, URA was given i.v. (0.25 + 0.25 + 0.50 + 1.0 mg/kg) in 15-min intervals. Following URA, the performance of the non-ischemic area was not systematically affected, but dLLAD increased by about 50%. This could neither be related to the significant reduction in afterload (AoP: -8%), nor to an increase in preload (LVedP and edLLAD did not change significantly), nor to an improved oxygen supply via the LAD (QLAD even decreased), although an increased collateral flow the LCA could not be excluded. The increase in systolic shortening correlated very closely to a decrease in heart rate (r = -0.92). It is concluded that the improved function of ischemic myocardium following urapidil resulted from a reduced oxygen demand in consequence to the decrease in heart rate.

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Section: Reduction Of Afterloadsupporting

confidence: 68%

Section: Introductionmentioning

confidence: 99%

Effect of urapidil on the performance of ischemic myocardium in anesthetized dogs

et al. 1990

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“…In some vessels it is reported to involve a direct action on 5-HT 1 -like or ß-adrenoceptors located on vascular smooth muscle cell itself [21]. In other arteries, 5-HT causes relaxation through release of endothelium-dependent relaxing factor (EDRF)-nitric oxide [5]. Many vasodilators cause vasodilatation by these mechanisms [22], however the ability of 5-HT to release nitric oxide from endothelium appears to be quite variable depending on both the site of origin of the artery and the species studied [23].…”

Section: Discussionmentioning

confidence: 99%

“…It causes vasodilata- Shingala/Balaraman tion partly by releasing nitric oxide from endothelial cells [3] and partly by inhibiting noradrenaline release from sympathetic nerve terminals. A number of 5-HT 1A receptor agonists such as 8-hydroxy-(2-N,N-dipropylamino)tetraline (8-OH-DPAT), flesinoxan [4] and urapidil [5] have been shown to lower blood pressure and reduce heart rate through a central action on sympathetic outflow (particularly renal sympathetic outflow) and cardiac vagal activity [6]. Flesinoxan is currently undergoing clinical trials, and many other agonists at this site are being explored as antihypertensive agents [4,5].…”

Section: Introductionmentioning

confidence: 99%

Antihypertensive Effect of 5-HT<sub>1A</sub> Agonist Buspirone and 5-HT<sub>2B</sub> Antagonists in Experimentally Induced Hypertension in Rats

Shingala

Balaraman²

2005

Pharmacology

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We investigated the antihypertensive effect of 5-HT_1A agonist (buspirone) and 5-HT_2B antagonists (SB204741 and SB200646) in deoxycorticosterone acetate (DOCA)-salt-induced hypertensive rats. Experiments were divided into two sets: in the first set, sham-operated control and DOCA-treated hypertensive rats received buspirone (1 mg/kg/day p.o. for 4 weeks) and in the second set, in vivo and in vitro studies were carried out. In the case of in vivo studies, sham-operated control and DOCA-treated hypertensive rats received SB204741 or SB200646 (1 mg/kg/week i.v. for 4 weeks). Blood pressure was measured weekly by tail-cuff method. After completion of the treatment schedule, blood pressure and vascular reactivity to various agonists like 5-HT, noradrenaline and adrenaline were recorded. Chronic administration of buspirone, SB204741 and SB200646 produced a significant reduction in blood pressure and vascular reactivity to agonists in DOCA-salt hypertensive rats, implying an antihypertensive effect. However, chronic administration of the same drugs in sham control rats did not alter blood pressure and vascular reactivity to various agonists. For in vitro studies a similar treatment schedule was followed as in vivo studies and a cumulative concentration response curve of 5-HT was recorded on isolated thoracic aorta. Treatment with 5-HT_2B antagonists shifted the concentration response curve of 5-HT to the right on isolated aorta. We conclude that 5-HT_1A agonist and 5-HT_2B antagonists possess an antihypertensive effect.

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“…Apart from its oq-antagonistic activity, urapidil displays significant centrally mediated antihypertensive potency, although the evidence for this mechanism is limited to animal experiments [31][32][33]. The central hypotensive mechanism of urapidil largely differs from that of clonidine, guanfacine and c~-methyldopa, which are known as the prototypes of centrally acting antihypertensives [34].…”

Section: Urapidilmentioning

confidence: 99%

Pharmacology of antihypertensive agents with multiple actions

Zwieten

1990

Eur J Clin Pharmacol

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Compounds with two or more different pharmacodynamic activities in a single molecule are designated as hybrid drugs. If several stereoisomers with different pharmacodynamic activities exist in one molecule, the term pseudo-hybrid drug is applied. In the treatment of hypertension, the use of hybrid drugs enables a considerable reduction in the number of tablets to be taken per day. Conversely, the dose of each individual component cannot be tritrated. Most hybrid drugs used in antihypertensive treatment are beta-blockers with an additional vasodilator component, caused by different mechanisms such as alpha-adrenoceptor blockade, beta 2-adrenoceptor agonism, ACE inhibition or direct relaxation of vascular smooth muscle. Examples include labetalol (in fact, a mixture of four stereoisomers), carvedilol, celiprolol, dilevalol, tertatolol and BWA-575 C. A combination of beta-receptor blockade and vasodilation may be beneficial from a hemodynamic point of view. More recently it has been recognized that urapidil and ketanserin are hybrid drugs, each containing at least two pharmacodynamic activities in their molecules.

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Experimental Studies on the Neurocardiovascular Effects of Urapidil

Cited by 38 publications

References 13 publications

Effect of urapidil on the performance of ischemic myocardium in anesthetized dogs

Effect of urapidil on the performance of ischemic myocardium in anesthetized dogs

Antihypertensive Effect of 5-HT<sub>1A</sub> Agonist Buspirone and 5-HT<sub>2B</sub> Antagonists in Experimentally Induced Hypertension in Rats

Pharmacology of antihypertensive agents with multiple actions

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