Serum dopamine β-hydroxylase activity in developing hypertensive rats

Nagatsu, Toshiharu; Kato, Takeshi; Numata, Yukiko; Ikuta, Kazunari; Umezawa, Hamao; Matsuzaki, M; Takeuchi, Tomio

doi:10.1038/251630a0

Cited by 84 publications

(21 citation statements)

References 7 publications

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“…In the present study, we examined the effects of PRO on bone status in SHR, a model of hypertension showing osteoporosis (Izawa et al, 1985;Barbagallo et al, 1991;Wang et al, 1993) with hyperactivity of the peripheral sympathetic tone (Nagatsu et al, 1971(Nagatsu et al, , 1974Klemola et al, 1999). In the literature, the antiosteoporotic effect of PRO was demonstrated recently in OVX rats treated with PRO at low doses (0.1-5 mg/kg/day) subcutaneously (Bonnet et al, 2006(Bonnet et al, , 2008, whereas the hypotensive effect of PRO was demonstrated previously in SHR treated orally with high-dose PRO (30 -100 mg/kg/day) (Takeda and Buñ ag, 1980;Antonaccio et al, 1986), suggesting that relatively low doses of PRO were adequate for antiosteoporotic action and high doses were adequate for antihypertensive action in rats.…”

Section: Discussionmentioning

confidence: 99%

“…SHR are characterized by elevated blood pressure, increased heart rate, raised plasma catecholamine level and dopamine ␤-hydroxylase activity, and increased adrenal tyrosine hydroxylase and dopamine ␤-hydroxylase activities compared with Wistar-Kyoto rats (WKY), a normotensive genetic control of SHR (Nagatsu et al, 1971(Nagatsu et al, , 1974Zhang and Thorén, 1998;Klemola et al, 1999), suggesting that the sympathetic nervous system of SHR is overactivated. SHR also showed reductions in cortical and cancellous bone mass and increases in bone turnover, suggesting that osteoporosis is developed in adult SHR (Izawa et al, 1985;Barbagallo et al, 1991;Wang et al, 1993).…”

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confidence: 99%

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Effects of Propranolol on Bone Metabolism in Spontaneously Hypertensive Rats

Sato

Arai²,

Goto³

et al. 2010

J Pharmacol Exp Ther

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The effects of propranolol (PRO), a nonselective ␤-adrenergic receptor (␤-AR) antagonist with membrane-stabilizing action on bone metabolism, were examined in spontaneously hypertensive rats (SHR) showing osteoporosis with hyperactivity of the sympathetic nervous system. Treatment of SHR with PRO at 1 and 5 mg/kg p.o. for 12 weeks increased bone mass of the lumbar vertebra and proximal tibia without affecting blood pressure, but PRO at 50 and 100 mg/kg with hypotensive action did not increase bone mass. Next, the effects of PRO at 0.1, 1, and 10 mg/kg on bone status were examined in more detail. Compared with the SHR control, not only bone mass but also biomechanical parameters of strength and toughness of the lumbar vertebrae were increased in SHR treated with PRO at 0.1 and 1 mg/kg, suggesting antiosteoporotic action. PRO at 1 mg/kg statistically increased histomorphometry indices of bone formation, whereas PRO at doses of 0.1, 1, and 10 mg/kg decreased those of bone resorption. Antiosteoporotic effect of PRO is attenuated at 10 mg/kg compared with 0.1 and 1 mg/kg. In addition, treatment with timolol, a nonselective ␤-AR antagonist without membrane-stabilizing action, or butoxamine, a selective ␤2-AR antagonist, at 1 mg/kg increased bone mass in SHR. These results suggested that treatment of SHR with ␤-blockers at low dose improved bone loss and bone fragility. This antiosteoporotic effect of ␤-blockers seems to be caused by the blocking action of ␤2-AR, regardless of the membrane-stabilizing action.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Effects of Propranolol on Bone Metabolism in Spontaneously Hypertensive Rats

Sato

Arai²,

Goto³

et al. 2010

J Pharmacol Exp Ther

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“…The degree of involvement of sympathetic nerves and the adrenal medulla may vary with different types of hypertension and during different phases of the development of experimental and human hypertension (Grobecker et al, 1975Saavedra et al, 1976Saavedra et al, , 1978). An increased sympathetic neuronal activity reflected by elevated circulating noradrenaline concentrations and dopamine-p-hydroxylase activity was demonstrated in young spontaneously hypertensive rats (Nagatsu et al, 1974;Grobecker et al, 0306-5251/82/130 381-10 $01.00 1975). Also in patients with essential hypertension a significant elevation of plasma catecholamines was found (for review see Axelrod, 1976).…”

Section: Introductionmentioning

confidence: 99%

Elevated plasma catecholamines in young hypertensive and hyperkinetic patients: effect of pindolol.

Dominiak¹,

Grobecker²

1982

Brit J Clinical Pharma

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1 The sympathetic nervous system plays an important role in the regulation of blood pressure. Plasma catecholamine concentrations are considered to be reliable indices of sympatho-neuronal (noradrenaline) and sympatho-adrenal (adrenaline) activity and reactivity in man. 2 Sympathetic and adrenal activity and reactivity in young patients with essential hypertension or hyperkinetic heart syndrome were compared with an appropriate control group matched for age. The groups of hypertensive patients and patients with hyperkinetic heart syndrome could be clearly distinguished from control subjects on the basis of circulating catecholamine levels at rest. 3 A clear-cut increase in circulating noradrenaline and adrenaline was observed in young patients with essential hypertension and hyperkinetic heart syndrome at rest. Clinically, hypertensive patients were characterized by elevated systolic and diastolic blood pressure and increased heart rate, whereas patients with hyperkinetic heart syndrome had increased heart rate and increased systolic blood pressure, whereas diastolic blood pressure was normal. At rest, there was a significant positive correlation between heart rate and circulating catecholamines in both groups of patients. In hypertensives a positive correlation between heart rate and plasma adrenaline concentrations, in patients with hyperkinetic heart syndrome a positive correlation between heart rate and plasma noradrenaline concentrations could be observed. In addition a positive correlation between plasma noradrenaline concentrations and systolic blood pressure in all groups of patients studied, was obtained. 4 Sympatho-neuronal and sympatho-adrenal reactivity during mental stress or physical exercise increased in both groups of patients, mirrored by an increase in blood pressure and heart rate.5 Pindolol, a potent non-selective P-adrenoceptor blocking drug with intrinsic sympathomimetic activity and minimal membrane stabilizing properties, administered in a single oral dose of 10 mg, diminished the exaggerated sympathetic tone in both groups of patients by attenuating circulating catecholamine levels at rest or during mental stress, but not during physical exercise.

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“…Spontaneously hypertensive rats (SHR) are characterized by increased blood pressure, heart rate, plasma catecholamine levels, and dopamine β-hydroxylase and adrenal tyrosine hydroxylase (TH) levels, which are markers of sympathetic nervous activity (Nagatsu et al, 1974;Zhang and Thorén, 1998;Klemola et al, 1999). In comparison with Wistar-Kyoto rats (WKY), considered normotensive genetic controls, SHR have an overactive sympathetic nervous system.…”

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confidence: 99%

Selective β2-adrenergic Antagonist Butoxamine Reduces Orthodontic Tooth Movement

et al. 2014

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Recently, involvement of the sympathetic nervous system in bone metabolism has attracted attention. β2-Adrenergic receptor (β2-AR) is presented on osteoblastic and osteoclastic cells. We previously demonstrated that β-AR blockers at low dose improve osteoporosis with hyperactivity of the sympathetic nervous system via β2-AR blocking, while they may have a somewhat inhibitory effect on osteoblastic activity at high doses. In this study, the effects of butoxamine (BUT), a specific β2-AR antagonist, on tooth movement were examined in spontaneously hypertensive rats (SHR) showing osteoporosis with hyperactivity of the sympathetic nervous system. We administered BUT (1 mg/kg) orally, and closed-coil springs were inserted into the upper-left first molar. After sacrifice, we calculated the amount of tooth movement and analyzed the trabecular microarchitecture and histomorphometry. The distance in the SHR control was greater than that in the Wistar-Kyoto rat group, but no significant difference was found in the SHR treated with BUT compared with the Wistar-Kyoto rat control. Analysis of bone volume per tissue volume, trabecular number, and osteoclast surface per bone surface in the alveolar bone showed clear bone loss by an increase of bone resorption in SHR. In addition, BUT treatment resulted in a recovery of alveolar bone loss. Furthermore, TH-immunoreactive nerves in the periodontal ligament were increased by tooth movement, and BUT administration decreased TH-immunoreactive nerves. These results suggest that BUT prevents alveolar bone loss and orthodontic tooth movement via β2-AR blocking.

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Serum dopamine β-hydroxylase activity in developing hypertensive rats

Cited by 84 publications

References 7 publications

Effects of Propranolol on Bone Metabolism in Spontaneously Hypertensive Rats

Effects of Propranolol on Bone Metabolism in Spontaneously Hypertensive Rats

Elevated plasma catecholamines in young hypertensive and hyperkinetic patients: effect of pindolol.

Selective β2-adrenergic Antagonist Butoxamine Reduces Orthodontic Tooth Movement

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