Effects of Several Beta-Blocking Agents on the Development of Hypertension in Spontaneously Hypertensive Rats

Takeda, Kazuki; Nakagawa, Yoshito; Hashimoto, Takehisa; Sakurai, Hiroshi; Imai, Shoichi

doi:10.1254/jjp.29.171

Cited by 15 publications

(1 citation statement)

References 23 publications

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“…The SHR strain has been utilized in numerous studies to evaluate the known or potential antihypertensive effect of agents and/or treatments. Antihypertensive drugs such as propranolol (Inderal ® , β‐adrenergic receptor antagonist), captopril (Capoten ® , angiotensin‐converting enzyme (ACE) inhibitor), and clonidine (Catapres ® , nonselective α 2 ‐adrenergic receptor agonist) lower blood pressure in the SHR (Ferrone and Antonaccio 1979; Goźlińska and Czyzewska‐Szafran 1999; Takeda et al 1979). While the latter agents are usually effective and tolerated to various degrees in humans, they can exert an array of side effects (e.g., Steiner 1988).…”

Section: Cardiovascular Assessment: Heart Rate (Hr) and Blood Pressurmentioning

confidence: 99%

TDIQ (5,6,7,8–tetrahydro‐1,3‐dioxolo [4,5‐g]isoquinoline): Discovery, Pharmacological Effects, and Therapeutic Potential

Young

2007

CNS Drug Reviews

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Chemically, TDIQ (5,6,7,8-tetrahydro-1,3-dioxolo[4,5-g]isoquinoline) can be viewed as a conformationally restricted phenylalkylamine that is related in structure to amphetamine but does not stimulate (or depress) locomotor activity in rodents. In radioligand binding studies TDIQ displays selective affinity for alpha(2)-adrenergic receptor subsites (i.e., alpha(2A)-, alpha(2B)-, and alpha(2C)-adrenergic receptors), and behavioral data suggest that it might exert an agonist (or partial agonist) effect at alpha(2)-adrenergic receptors or interact at alpha(2)-adrenergic heteroreceptors. Drug discrimination studies in rats indicate that TDIQ: (1) serves as a discriminative stimulus, (2) may be useful in the treatment of symptoms associated with the abuse of cocaine, and (3) exhibits a low potential for abuse. In addition, TDIQ exhibits a dose-dependent and wide dissociation between doses that produce an anxiolytic-like effect or an inhibition of "snack" consumption in mice and doses that produce minimal, if any, effects in tests that measure a potential for disruption of coordinated movement or motor activity. Also, TDIQ displays negligible effects on the heart rate (HR) and blood pressure (BP) of mice. Taken together, the preclinical data suggest that TDIQ exhibits a favorable ratio of therapeutic-like effects (anxiolytic, therapeutic adjunct in the treatment of cocaine abuse, and appetite suppression) to side effect-like activities (behavioral impairment, drug abuse, or adverse cardiovascular effect). As such, TDIQ could: (1) be a forerunner for a new type of chemical entity in the treatment of certain forms of anxiety and/or obesity and (2) serve as a structural template in the discovery and development of additional agents that might be selective for alpha(2)-adrenergic receptors.

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Section: Cardiovascular Assessment: Heart Rate (Hr) and Blood Pressurmentioning

confidence: 99%

TDIQ (5,6,7,8–tetrahydro‐1,3‐dioxolo [4,5‐g]isoquinoline): Discovery, Pharmacological Effects, and Therapeutic Potential

Young

2007

CNS Drug Reviews

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Role of ?2-adrenoceptor blockade and circulating adrenaline level for the pressor responses to ?-adrenoceptor blocking drugs in rats

Himori¹,

Ishimori²,

Shiratsuchi³

et al. 1984

Naunyn-Schmiedeberg's Arch. Pharmacol.

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The present experiments were designed to elucidate what mechanism(s) would be responsible for beta-adrenoceptor blocking drugs (beta-blockers)-induced pressor responses in rats. In urethane-anaesthetized rats, 6 beta-blockers at i.v. doses ranging from 0.3 to 300 micrograms/kg evoked the pressor response in a dose-dependent manner. The relative potency in causing the pressor action was correlated not to their beta 1-blocking activities (r = 0.374, P greater than 0.05) but to their beta 2-blocking ones (r = 0.856, P less than 0.05). In pithed or adrenalectomized rats with low levels of plasma catecholamines, however, propranolol failed to exert its sustained pressor action. Propranolol (300 micrograms/kg i.v.) distinctly potentiated the pressor responses not to noradrenaline but to adrenaline and to electrical stimulation of the sympathetic outflow (E.S.) in pithed rats. On the contrary, there was not any potentiation of pressor response to E.S. in pithed, adrenalectomized rats treated with propranolol (300 micrograms/kg i.v.). In rats treated with phenoxybenzamine (5 mg/kg i.v.), adrenaline was shown to have much more potent vasodilating action resulting from beta 2-stimulation than noradrenaline, the dose difference for causing the diastolic blood pressure decrease by a 25 mm Hg being almost 80 times. In pithed rats, infusion of adrenaline at the rate of 0.02 micrograms/min caused a significant increase in plasma adrenaline level from 0.02 +/- 0.01 to 0.45 +/- 0.048 ng/ml, being close to basal level obtained in urethane-anaesthetized rats. Under this situation, propranolol (1-100 micrograms/kg i.v.) showed a distinct pressor response in a dose-dependent fashion as observed in adrenal intact rats anaesthetized with urethane.(ABSTRACT TRUNCATED AT 250 WORDS)

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Amelioration of genetic (SHR) hypertension: A consequence of early handling

Tang

Gandelman

Falk

1982

Physiology & Behavior

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Effects of Several Beta-Blocking Agents on the Development of Hypertension in Spontaneously Hypertensive Rats

Cited by 15 publications

References 23 publications

TDIQ (5,6,7,8–tetrahydro‐1,3‐dioxolo [4,5‐g]isoquinoline): Discovery, Pharmacological Effects, and Therapeutic Potential

TDIQ (5,6,7,8–tetrahydro‐1,3‐dioxolo [4,5‐g]isoquinoline): Discovery, Pharmacological Effects, and Therapeutic Potential

Role of ?2-adrenoceptor blockade and circulating adrenaline level for the pressor responses to ?-adrenoceptor blocking drugs in rats

Amelioration of genetic (SHR) hypertension: A consequence of early handling

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