Clonidine Improves Central Attenuation of the Baroreflex in Spontaneously Hypertensive Rats.

Hayashi, Junko; Takeda, Kazuo; Kuwabara, Tadao; Takesako, Toshiyuki; Itoh, Hiroshi; Hirata, Masahiro; Tanabe, Shingo; Nakata, Tetsuo; Sasaki, Susumu; Nakagawa, Masao

doi:10.1536/ihj.34.333

Cited by 11 publications

(12 citation statements)

References 18 publications

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“…Before experimental intervention, we observed a significantly higher resting blood pressure and an upward resetting of baroreflex function in SHR relative to age-matched WKY. As previously described by others, the baroreflex control of MAP in SHR paralleled that in WKY, with similar absolute decline in MAP during ADN stimulation (9,12), but baroreflex control of RSNA and HR was attenuated (4,9,12,15,24,34). These alterations in baroreflex function in the SHR have been associated with a reduction in both catecholamine content in the NTS and ␣ 2 -adrenoreceptor numbers within the NTS (27,36,37).…”

Section: Discussionsupporting

confidence: 76%

“…In the spontaneously hypertensive rat (SHR), for example, resting blood pressure may be 40-60 mmHg higher than in normotensive rats, and the sigmoid curve describing baroreflex control of mean arterial pressure (MAP) and sympathetic nerve activity is shifted upward but remains parallel to the normal baroreflex curve (9,12,38). In contrast, baroreflex control of heart rate (HR) is markedly attenuated in the SHR (2,15,21,34), despite a resting HR that is comparable to that of its normotensive control, the Wistar-Kyoto rat (WKY).…”

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confidence: 99%

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α₂-Adrenergic receptors in NTS facilitate baroreflex function in adult spontaneously hypertensive rats

Hayward

Riley

Felder

2002

American Journal of Physiology-Heart and Circulatory Physiology

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We examined the effect of ␣2-adrenoreceptor blockade in the nucleus of the solitary tract (NTS) on baroreflex responses elicited by electrical stimulation of the left aortic depressor nerve (ADN) in urethane-anesthetized spontaneously hypertensive rats (SHR, n ϭ 11) and normotensive Wistar-Kyoto rats (WKY, n ϭ 11). ADN stimulation produced a frequencydependent decrease in mean arterial pressure (MAP), renal sympathetic nerve activity (RSNA), and heart rate (HR). In SHR, unilateral microinjection of idazoxan into the NTS markedly reduced baroreflex control of MAP, RSNA, and HR and had a disproportionately greater influence on baroreflex control of MAP than of RSNA. In WKY, idazoxan microinjections did not significantly alter baroreflex function relative to control vehicle injections. These results suggest that baroreflex regulation of arterial pressure in SHR is highly dependent on NTS adrenergic mechanisms. The reflex regulation of sympathetic outflow to the kidney is less influenced by the altered ␣ 2-adrenoreceptor mechanisms in SHR.hypertension; medulla; norepinephrine IN HYPERTENSION, the arterial baroreflex is often characterized by a decrease in reflex sensitivity and/or a resetting of reflex function to higher than normal pressures (9,10,15,31,34). In the spontaneously hypertensive rat (SHR), for example, resting blood pressure may be 40-60 mmHg higher than in normotensive rats, and the sigmoid curve describing baroreflex control of mean arterial pressure (MAP) and sympathetic nerve activity is shifted upward but remains parallel to the normal baroreflex curve (9,12,38). In contrast, baroreflex control of heart rate (HR) is markedly attenuated in the SHR (2, 15, 21, 34), despite a resting HR that is comparable to that of its normotensive control, the Wistar-Kyoto rat (WKY). Because baroreflex impairment is present in many forms of hypertension and may contribute to the development and maintenance of the disease (9,10,15,31,34), an understanding of the neurochemical mechanisms involved is of great importance. Neurochemical derangements in hypertension might alter afferent and efferent signaling or integration of baroreceptor information within the central nervous system.In the brain, the medial nucleus of the solitary tract (NTS) in the caudal medulla is the primary central termination site for baroreceptor afferents (16). The integrity of this region is necessary for normal baroreflex control of blood pressure (29). In the SHR and other rat models of hypertension with altered baroreflex function, declines in norepinephrine content and ␣ 2 -adrenoreceptor density within the NTS have been documented (27,33,36,37). Because selective blockade of ␣ 2 -adrenoreceptors in the medial NTS of normotensive subjects can increase resting blood pressure and attenuate baroreflex function (19,30,35), this decline in ␣ 2 -adrenoreceptor density in the NTS of hypertensive animals has been hypothesized to contribute to autonomic dysfunction in these animals. However, the physiological impact of these neurochemical changes o...

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Section: Discussionsupporting

confidence: 76%

mentioning

confidence: 99%

α₂-Adrenergic receptors in NTS facilitate baroreflex function in adult spontaneously hypertensive rats

Hayward

Riley

Felder

2002

American Journal of Physiology-Heart and Circulatory Physiology

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“…14 Therefore, Bj-PRO-10c-induced decreases of MAP and HR could result from interference of Bj-PRO-10c with the autonomic nervous system, provoking changes in HR and baroreflex control. 15,16 Arterial baroreflex is one of the most important regulatory mechanisms in the cardiovascular system. Baroreflex function, expressed as baroreflex sensitivity, is measured to assess autonomic control.…”

Section: Introductionmentioning

confidence: 99%

Brain nitric oxide production by a proline-rich decapeptide from Bothrops jararaca venom improves baroreflex sensitivity of spontaneously hypertensive rats

Lameu

Pontieri

Guerreiro³

et al. 2010

Hypertens Res

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Baroreflex sensitivity is disturbed in many people with cardiovascular diseases such as hypertension. Brain deficiency of nitric oxide (NO), which is synthesized by NO synthase (NOS) in the citrulline-NO cycle (with argininosuccinate synthase (ASS) activity being the rate-limiting step), contributes to impaired baroreflex. We recently showed that a decapeptide isolated from Bothrops jararaca snake venom, denoted Bj-PRO-10c, exerts powerful and sustained antihypertensive activity. Bj-PRO-10c promoted vasodilatation dependent on the positive modulation of ASS activity and NO production in the endothelium, and also acted on the central nervous system, inducing the release of GABA and glutamate, two important neurotransmitters in the regulation of autonomic systems. We evaluated baroreflex function using the regression line obtained by the best-fit points of measured heart rate (HR) and mean arterial pressure (MAP) data from spontaneously hypertensive rats (SHRs) treated with Bj-PRO-10c. We also investigated molecular mechanisms involved in this effect, both in vitro and in vivo. Bj-PRO-10c mediated an increase in baroreflex sensitivity and a decrease in MAP and HR. The effects exerted by the peptide include an increase in the gene expression of endothelial NOS and ASS. Bj-PRO-10c-induced NO production depended on intracellular calcium fluxes and the activation of a G i/o -protein-coupled metabotropic receptor. Bj-PRO-10c induced NO production and the gene expression of ASS and endothelial NOS in the brains of SHRs, thereby improving baroreflex sensitivity. Bj-PRO-10c may reveal novel approaches for treating diseases with impaired baroreflex function. Hypertension Research (2010Research ( ) 33, 1283Research ( -1288 doi:10.1038/hr.2010 Keywords: argininosuccinate synthase; baroreflex sensitivity; Bothrops jararaca venom; nitric oxide; proline-rich oligopeptide INTRODUCTIONThe gaseous messenger NO is involved mainly in the regulation of local and systemic vascular resistance, sodium balance and, consequently, blood pressure control, 1 but it is also a signaling molecule and modulator of brain function. 2 Recent studies relate NO with central cardiovascular control through the regulation of the cardiac and vascular autonomic system via the modulation of the central sites of cardiovascular autonomic neural integration. 3,4 NO is generated in the citrulline-NO cycle by NO synthase (NOS) using L-arginine as a substrate. Three isoforms of NOS have been described: calcium-dependent endothelial (eNOS) and neuronal (nNOS) isoforms and inducible NOS. The expression and activity

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“…However, baroreflex sensitivity was consistently suppressed by epidural lidocaine at all concentrations of isoflurane. This difference may be due to the fact that the sites act differently between epidural clonidine and epidural lidocaine, although there is a potential for a Type II statistical error due to the small sample size in this study, and species effects are likely (15)(16)(17)(18)(19)(20)(21)(22). The sites of epidural clonidine to act are still controversial.…”

Section: Discussionmentioning

confidence: 83%

“…The effects of systemic administration of clonidine on baroreflex regulation differ from study to study, depending on species, background anesthesia, and presence or absence of hypertension (15)(16)(17)(18)(19)(20)(21). However, intrathecal administration of clonidine attenuates baroreflexes in awake sheep by sympatholysis at spinal sites (22).…”

mentioning

confidence: 99%

Epidural Clonidine Suppresses the Baroreceptor-Sympathetic Response Depending on Isoflurane Concentrations in Cats

Ikeda

Nishikawa²,

Ohashi³

et al. 2003

Anesthesia & Analgesia

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Epidural administration of clonidine induces hypotension and bradycardia secondary to decreased sympathetic nerve activity. In this study, we sought to elucidate the change in baroreflex response caused by epidural clonidine. Thirty-six cats were allocated to six groups (n = 6 each) and were given either thoracic epidural clonidine 4 micro g/kg or lidocaine 2 mg/kg during 0.5, 1.0, or 1.5 minimum alveolar anesthetic concentration (MAC) isoflurane anesthesia. Heart rate (HR), mean arterial blood pressure (MAP), and cardiac sympathetic nerve activity (CSNA) were measured. Depressor and pressor responses were induced by IV nitroprusside 10 micro g/kg and phenylephrine 10 micro g/kg, respectively. Baroreflex was evaluated by the change in both CSNA and HR relative to the peak change in MAP (deltaCSNA/deltaMAP and deltaHR/deltaMAP, respectively). These measurements were performed before and 30 min after epidural drug administration. Epidural clonidine and lidocaine decreased HR, MAP, and CSNA by similar extents. deltaCSNA/deltaMAP and deltaHR/deltaMAP for depressor response were suppressed with epidural lidocaine and clonidine in all groups but the clonidine 0.5 MAC isoflurane group (0.197 +/- 0.053 to 0.063 +/- 0.014 and 0.717 +/- 0.156 to 0.177 +/- 0.038, respectively, by epidural lidocaine [P < 0.05] but 0.221 +/- 0.028 to 0.164 +/- 0.041 and 0.721 +/- 0.177 to 0.945 +/- 0.239, respectively, by epidural clonidine during 0.5 MAC isoflurane). Those for pressor response were suppressed in all groups. We conclude that thoracic epidural clonidine suppresses baroreflex gain during isoflurane anesthesia >1.0 MAC but may offer certain advantages compared with epidural lidocaine during 0.5 MAC isoflurane by virtue of preserving baroreflex sensitivity when inadvertent hypotension occurs.

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Clonidine Improves Central Attenuation of the Baroreflex in Spontaneously Hypertensive Rats.

Cited by 11 publications

References 18 publications

α₂-Adrenergic receptors in NTS facilitate baroreflex function in adult spontaneously hypertensive rats

α₂-Adrenergic receptors in NTS facilitate baroreflex function in adult spontaneously hypertensive rats

Brain nitric oxide production by a proline-rich decapeptide from Bothrops jararaca venom improves baroreflex sensitivity of spontaneously hypertensive rats

Epidural Clonidine Suppresses the Baroreceptor-Sympathetic Response Depending on Isoflurane Concentrations in Cats

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Clonidine Improves Central Attenuation of the Baroreflex in Spontaneously Hypertensive Rats.

Cited by 11 publications

References 18 publications

α2-Adrenergic receptors in NTS facilitate baroreflex function in adult spontaneously hypertensive rats

α2-Adrenergic receptors in NTS facilitate baroreflex function in adult spontaneously hypertensive rats

Brain nitric oxide production by a proline-rich decapeptide from Bothrops jararaca venom improves baroreflex sensitivity of spontaneously hypertensive rats

Epidural Clonidine Suppresses the Baroreceptor-Sympathetic Response Depending on Isoflurane Concentrations in Cats

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α₂-Adrenergic receptors in NTS facilitate baroreflex function in adult spontaneously hypertensive rats

α₂-Adrenergic receptors in NTS facilitate baroreflex function in adult spontaneously hypertensive rats