BLOOD PRESSURE VARIABILITY, CARDIAC BAROREFLEX SENSITIVITY and ORGAN DAMAGE IN EXPERIMENTALLY HYPERTENSIVE RATS

Wang, Di-Song; Xie, He-Hui; Shen, Fu‐Ming; Cai, Guo-Jun; Su, Ding‐Feng

doi:10.1111/j.1440-1681.2005.04229.x

Cited by 32 publications

(32 citation statements)

References 26 publications

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“…The elevation in heart rate of the DOCA-salt rats was not greater than the sham rats, although the blood pressure fall was greater. One explanation for this is the observed depression of baroreflex sensitivity in the DOCA-salt model (Wang et al, 2005). Although blood pressure remained reduced in the sham and DOCA-salt rats administered 5-HT when compared with control, it seemed clear that blood pressure recovered to a degree.…”

Section: Discussionmentioning

confidence: 94%

5-Hydroxytryptamine Lowers Blood Pressure in Normotensive and Hypertensive Rats

Diaz

Thompson

et al. 2008

J Pharmacol Exp Ther

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Arterial hyper-responsiveness to 5-hydroxytryptamine (5-HT) is a hallmark of hypertension, and plasma levels of free 5-HT are elevated in hypertension. We hypothesized that chronic administration of 5-HT would cause blood pressure to 1) rise in normotensive rats and 2) rise significantly more in hypertensive rats. The deoxycorticosterone acetate (DOCA)-salt hypertensive and sham normotensive rat were used. Animals were implanted with minipumps that delivered 5-HT (or vehicle) at a rate of 25 g/kg/min for 7 days. Free plasma 5-HT was elevated significantly by this protocol. Within 48 h, mean arterial blood pressure measured telemetrically decreased in sham (106 Ϯ 2 to 83 Ϯ 2 mm Hg) and in DOCA-salt hypertensive (166 Ϯ 9 to 112 Ϯ 3 mm Hg) rats; vehicle did not change blood pressure in either group. Ganglionic blockade (hexamethonium) reduced blood pressure to a greater magnitude in DOCA vehicle-administered rats (peak fall arterial pressure, 91 Ϯ 14 mm Hg) compared with DOCA 5-HT-administered rats (40 Ϯ 6 mm Hg). Maximal acetylcholine-induced (NO-dependent) relaxation in phenylephrine-contracted aortic strips was greater in 5-HTadministered (69.2 Ϯ 9.1% relaxation) versus vehicle-administered (39.7 Ϯ 14.2%) DOCA rats; aortic endothelial cell nitric oxide synthase expression was higher in the 5-HT-versus vehicle-administered DOCA-salt rats. In normotensive and DOCAsalt hypertensive rats, the nitric oxide synthase (NOS) inhibitor N -nitro-L-arginine (0.5 g/l in water) prevented the fall in blood pressure to 5-HT. We conclude that chronic exogenous 5-HT reduces blood pressure in normotensive and hypertensive rats through mechanisms critically dependent on NOS.Serotonin [5-hydroxytryptamine (5-HT)] was discovered and characterized over 60 years ago by the Italian scientist Erspamer (Erspamer and Asero, 1952) and by Irving Page (Rapport et al., 1948; Page and McCubbin, 1953a,b). In the periphery, 5-HT is made primarily in the enterochromaffin cells of the intestine. The circulatory system is exposed to 5-HT through aggregation of platelets (which take up and store a millimolar concentration of 5-HT), release from adrenergic nerves that have taken up 5-HT, and through direct exposure to 5-HT that is free in the blood. In many tissues, 5-HT is taken up and concentrated by the serotonin transporter (SERT) and is rapidly metabolized to an inactive metabolite, 5-hydroxyindole acetic acid (5-HIAA), by intracellular monoamine oxidase.5-HT was originally described as a substance derived from serum (sero) that increased the tone of smooth muscle (tonin). Because of the close association of the platelet with the blood vessel, there has been a long-standing question as to the role of 5-HT in controlling vascular tone and modifying blood pressure under normotensive and hypertensive conditions. Several findings suggest that 5-HT contributes to systemic hypertension. These include the following findings: 1) plasma levels (free) of 5-HT are elevated in experimental and human models of hypertension (Fetkovska et al., 1990;Carr...

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Section: Discussionmentioning

confidence: 94%

5-Hydroxytryptamine Lowers Blood Pressure in Normotensive and Hypertensive Rats

Diaz

Thompson

et al. 2008

J Pharmacol Exp Ther

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“…*P < 0.01 vs sham-operated group 4 Pre-atropine (unpaired t-test); †P < 0.01 vs SBP-above (paired t-test); ‡P < 0.01, § P < 5 0.05 vs Pre-atropine (paired t-test); ||P < 0.01 vs WKY (unpaired t-test). SBP-above, 6 Systolic blood pressure measured at carotid artery; SBP-below, Systolic blood pressure 7 measured at abdominal aorta; HR, heart rate; bpm, beats per minute; Sham, 8 sham-operated rats; CH, coarctation hypertensive rats. 9 …”

Section: Atropine (Ivmentioning

confidence: 99%

“…2,3 Furthermore, the reninangiotensin system can contribute to EOD, at least partly by promoting inflammation. 4 -7 However, cardiovascular inflammation and EOD can also occur without renin-angiotensin system activation, 8 so other mechanisms must also operate.…”

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confidence: 99%

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Dysfunction of the Cholinergic Anti-Inflammatory Pathway Mediates Organ Damage in Hypertension

et al. 2011

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Abstract-Inflammatory responses are associated with the genesis and progression of end-organ damage (EOD) in hypertension. A role for the ␣7 nicotinic acetylcholine receptor (␣7nAChR) in inflammation has recently been identified. We tested the hypothesis that ␣7nAChR dysfunction contributes to hypertensive EOD. In both spontaneously hypertensive rats (SHRs) and rats with abdominal aorta coarctation-induced hypertension, atropine-induced tachycardia was blunted compared with normotensive controls. Both models of hypertension were associated with deficits in expression of the vesicular acetylcholine transporter and the ␣7nAChR in cardiovascular tissues. In hypertension induced by abdominal aorta coarctation, deficits in aortic vesicular acetylcholine transporter and ␣7nAChR were present both above and below the coarctation site, indicating that they were independent of the level of arterial pressure itself. Hypertension in 40-week-old SHRs was associated with cardiac and aortic hypertrophy. Morphological abnormalities consistent with EOD, along with elevated tissue levels of proinflammatory cytokines (tumor necrosis factor-␣, interleukin-1␤, and interleukin-6) were observed in the heart, kidney, and aorta. Chronic treatment of SHRs with the ␣7nAChR agonist PNU-282987 relieved EOD and inhibited tissue levels of proinflammatory cytokines and activation of nuclear factor B. Greater serum levels of proinflammatory cytokines and more severe damage in the heart, aorta, and kidney were seen in ␣7nAChR Ϫ/Ϫ mice subjected to 2-kidney-1-clip surgery than in wild-type mice. A deficit in the cholinergic anti-inflammatory pathway appears to contribute to the pathogenesis of EOD in models of hypertension of varying etiology. This pathway may provide a new target for preventing cardiovascular disease resulting from hypertension. (Hypertension. 2011;57:298-307.) • Online Data Supplement Key Words: acetylcholine Ⅲ ␣7 nicotinic acetylcholine receptor Ⅲ inflammation Ⅲ hypertension Ⅲ end-organ damage H ypertension is a major risk factor for myocardial infarction, heart failure, stroke, and kidney dysfunction. Endorgan damage (EOD), including cardiac hypertrophy and myocyte dysfunction, vascular remodeling, and renal lesions, is a crucial mediatory link between hypertension and the development of these cardiovascular events. 1 Therefore, a better understanding of the mechanisms leading to hypertensive EOD could provide new avenues for prevention of cardiovascular events. Inflammation is very important in the genesis and development of EOD. 2,3 Furthermore, the reninangiotensin system can contribute to EOD, at least partly by promoting inflammation. 4 -7 However, cardiovascular inflammation and EOD can also occur without renin-angiotensin system activation, 8 so other mechanisms must also operate.Recent evidence indicates that neuronal 9 -11 cholinergic systems influence inflammatory responses by controlling the release of tumor necrosis factor (TNF)-␣, interleukin-(⌱L)-1␤, and IL-6 and that nonneuronal acetylcholine synthesis and rele...

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“…ABR function is impaired in hypertension, heart failure, and diabetes and has been found to be a crucial determinant of sudden death after acute myocardial infarction [24] . In hypertensive rats, the target organ damage correlates negatively with ABR function [10,25] . Interruption of ABR by sinoaortic denervation induced aortic and cardiac hypertrophy independent of the mean level of blood pressure [26][27][28] .…”

Section: Discussionmentioning

confidence: 99%

Circadian expression of clock genes and angiotensin II type 1 receptors in suprachiasmatic nuclei of sinoaortic-denervated rats

Sun

Wang

et al. 2007

Acta Pharmacologica Sinica

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Aim: To investigate whether the circadian expression of central clock genes and angiotensin II type 1 (AT1) receptors was altered in sinoaortic‐denervated (SAD) rats. Methods: Male Sprague‐Dawley rats underwent sinoaortic denervation or a sham operation at the age of 12 weeks. Four weeks after the operation, blood pressure and heart period were measured in the conscious state in a group of sham‐operated (n=10) and SAD rats (n=9). Rest SAD and sham‐operated rats were divided into 6 groups (n=6 in each group). The suprachiasmatic nuclei (SCN) tissues were taken every 4 h throughout the day from each group for the determination of the mRNA expression of clock genes (Per2 and Bmal1) and the AT1 receptor by RT‐PCR; the protein expression of Per2 and Bmal1 was determined by Western blotting. Results: Blood pressure levels in the SAD rats were similar to those of the sham‐operated rats. However, blood pressure variabilities significantly increased in the SAD rats compared with the sham‐operated rats. The circadian variation of clock genes in the SCN of the sham‐operated rats was characterized by a marked increase in the mRNA and protein expression during dark periods. Per2 and Bmal1 mRNA levels were significantly lower in the SAD rats, especially during dark periods. Western blot analysis confirmed an attenuation of the circadian rhythm of the 2 clock proteins in the SCN of the SAD rats. AT1 receptor mRNA expressions in the SCN were abnormally upregulated in the light phase, changed to a 12‐h cycle in the SAD rats. Conclusion: The circadian variation of the 2 central clock genes was attenuated in the SAD rats. Arterial baroreflex dysfunction also induced a disturbance in the expression of AT1 receptors in the SCN.

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BLOOD PRESSURE VARIABILITY, CARDIAC BAROREFLEX SENSITIVITY and ORGAN DAMAGE IN EXPERIMENTALLY HYPERTENSIVE RATS

Cited by 32 publications

References 26 publications

5-Hydroxytryptamine Lowers Blood Pressure in Normotensive and Hypertensive Rats

5-Hydroxytryptamine Lowers Blood Pressure in Normotensive and Hypertensive Rats

Dysfunction of the Cholinergic Anti-Inflammatory Pathway Mediates Organ Damage in Hypertension

Circadian expression of clock genes and angiotensin II type 1 receptors in suprachiasmatic nuclei of sinoaortic-denervated rats

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