α-Adrenoceptors and vascular regulation: Molecular, pharmacologic and clinical correlates

Piascik, Michael T.; Soltis, Edward E.; Piascik, Mary M.; MacMillan, Leigh B.

doi:10.1016/s0163-7258(96)00117-9

Cited by 87 publications

(52 citation statements)

References 184 publications

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“…Theophylline, being a PDE inhibitor, is expected to increase cAMP (Somerville, 2001). By contrast, clonidine lowers blood pressure and heart rate by activating central G ␣i -coupled ␣ 2A receptors, causing a reduction in cAMP (Piascik et al, 1996). Although we used a dose (10 mg/kg) of theophylline that is The number of rats in each group is shown in parentheses.…”

Section: Discussionmentioning

confidence: 99%

Central Adenosine Signaling Plays a Key Role in Centrally Mediated Hypotension in Conscious Aortic Barodenervated Rats

Nassar¹,

Abdel‐Rahman²

2006

J Pharmacol Exp Ther

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We tested the hypothesis that clonidine-evoked hypotension is dependent on central adenosinergic pathways. Five groups of male, conscious, aortic baroreceptor-denervated (ABD) rats received clonidine (10 g/kg i.v.) 30 min after i.v. 1) saline, 2) theophylline (10 mg/kg), or 3) 8-(p-sulfophenyl)theophylline (8-SPT) (2.5 mg/kg) or 1 h after i.p. 4) dipyridamole (5 mg/kg) or 5) an equal volume of sesame oil. Blockade of central (theophylline) but not peripheral (8-SPT) adenosine receptors abolished clonidine hypotension. In contrast, dipyridamole substantially enhanced the bradycardic response to clonidine. In additional groups, intracisternal (i.c.) dipyridamole (150 g) and 8-SPT (10 g) enhanced and abolished, respectively, clonidine (0.6 g i.c.)-evoked hypotension. Because clonidine is a mixed I 1 /␣ 2 agonist, we also investigated whether adenosine signaling is linked to the I 1 or the ␣ 2A receptor by administering the selec- The mechanism of the centrally mediated hypotension elicited by clonidine and similar drugs is not fully understood. Reported studies have identified the brainstem and, in particular, the rostral ventrolateral medulla (RVLM), as the major neuroanatomical substrate for clonidine (Tingley and Arneric, 1990;Ernsberger and Haxhiu, 1997). Suppression of the activity of sympathetic neurons in the RVLM, assessed electrochemically (Mao et al., 2003) and electrophysiologically (Wang et al., 2004b), plays a crucial role in the hypotensive response elicited by clonidine. The dependence of clonidine-evoked hypotension on central neurotransmitters/ neuromodulators that directly or indirectly influence the activity of sympathetic neurons in the RVLM has enhanced our knowledge of the pharmacology of this class of drugs as well as central control of blood pressure (Wang et al., 2003(Wang et al., , 2004a.It is imperative to note, however, that the expression of the hypotensive effect of clonidine is dependent on the preparation used. Whereas clonidine-evoked hypotension manifests in hypertensive rats, conscious or anesthetized (Jastrzebski et al., 1995;Estato et al., 2004), it only manifests in anesthetized, but not conscious, normotensive rats (El-Mas et al., 1994;Yang et al., 2005). Reported studies including ours have shown that partial or complete baroreceptor denervation unmasks the hypotensive effect of clonidine in conscious normotensive rats (Abdel-Rahman, 1992; El-Mas and AbdelRahman, 1997;Medvedev et al., 1998). Up-regulation of the I 1 -and ␣ 2 -adrenergic receptors in the brainstem of aortic barodenervated rats has been reported in previous studies from our laboratory Abdel-Rahman, 1995, 1997). However, the mechanisms that underlie the enhancement of clonidine-evoked hypotension in this model are not fully understood. We focused on central adenosine signaling

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Section: Discussionmentioning

confidence: 99%

Central Adenosine Signaling Plays a Key Role in Centrally Mediated Hypotension in Conscious Aortic Barodenervated Rats

Nassar¹,

Abdel‐Rahman²

2006

J Pharmacol Exp Ther

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“…Vascular hyporesponsiveness and diminished vascular contractility are the pathophysiological hallmarks for the development and maintenance of arterial vasodilation, which is a strong independent predictor of survival in cirrhosis [27]. The SNS mediates its vasoconstrictor action predominantly via the a 1 -adrenoceptor which represents the primary mechanism by which it controls total peripheral resistance [28]. In fact, in the mesenteric arterial bed in humans as well as in the animal species used in our experiments, vasoconstriction induced by neuronally released norepinephrine is largely mediated by activation of postsynaptic a 1 -adrenoreceptors [28,29].…”

Section: Discussionmentioning

confidence: 99%

Enhanced Y1-receptor-mediated vasoconstrictive action of neuropeptide Y (NPY) in superior mesenteric arteries in portal hypertension

Wiest

Jurzik

Moleda

et al. 2006

Journal of Hepatology

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“…The pharmacological profile of the new compounds was evaluated by radioligand-binding assays ( It is known that a 1 -AR play many roles in the myocardium ranging from positive inotropic and chronotropic effects, through ischemic preconditioning to arrhythmogenesis and cardiac hypertrophy [21,22]. For example, the nonselective and selective a-adrenoceptor antagonist (phentolamine and prazosin) abanoquil, a highly selective a 1A -receptor blocker, prevented arrhythmias induced by adrenaline or cocaine infusions [24,24].…”

Section: Pharmacologymentioning

confidence: 99%

Synthesis and Pharmacological Evaluation of New 1‐[3‐(4‐Arylpiperazin‐1‐yl)‐2‐hydroxypropyl]‐pyrrolidin‐2‐one Derivatives with Anti‐arrhythmic, Hypotensive, and α‐Adrenolytic Activity

Kulig

Sapa

Maciąg

et al. 2007

Archiv der Pharmazie

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A series of novel arylpiperazines bearing a pyrrolidin-2-one fragment was synthesized and evaluated for the binding affinity of the alpha(1)- and alpha(2)-adrenoceptors (AR) and for the antiarrhythmic and hypotensive activities of the compounds. The most potent and selective compound 1-[2-hydroxy-3-[4-[(2-hydroxyphenyl)piperazin-1-yl]propyl]pyrrolidin-2-one 8 binds with pK(i) = 6.71 for alpha(1)-AR. Derivative 8 was also the most active in the prophylactic antiarrhythmic test in adrenaline-induced arrhythmia in anaesthetized rats. Its ED(50 )value equals 1.9 mg/kg (i.v.). Compounds with substituents such as a fluorine atom 4, a methyl 5, or a hydroxyl 8 group, or two substituents such as fluorine/chlorine atoms and methoxy groups in the phenyl ring, significantly decreased the systolic and diastolic pressure in normotensive anesthetized rats at a dosages of 5-10 mg/kg (i.v.). It was found that the presence of the piperazine ring and a hydroxy group in the second position of the propyl chain are critical structural features in determining the affinity of the compounds tested.

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α-Adrenoceptors and vascular regulation: Molecular, pharmacologic and clinical correlates

Cited by 87 publications

References 184 publications

Central Adenosine Signaling Plays a Key Role in Centrally Mediated Hypotension in Conscious Aortic Barodenervated Rats

Central Adenosine Signaling Plays a Key Role in Centrally Mediated Hypotension in Conscious Aortic Barodenervated Rats

Enhanced Y1-receptor-mediated vasoconstrictive action of neuropeptide Y (NPY) in superior mesenteric arteries in portal hypertension

Synthesis and Pharmacological Evaluation of New 1‐[3‐(4‐Arylpiperazin‐1‐yl)‐2‐hydroxypropyl]‐pyrrolidin‐2‐one Derivatives with Anti‐arrhythmic, Hypotensive, and α‐Adrenolytic Activity

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