Functional Arterial Baroreflex Attenuates the Effects of Antihypertensive Drugs in Conscious Rats

Wang, Jin; Shen, Fu‐Ming; Zhang, Xiaofei; Wang, Minwei; Su, Ding‐Feng

doi:10.1254/jphs.fp0050789

Cited by 4 publications

(5 citation statements)

References 22 publications

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“…Systolic BP (SBP), diastolic BP (DBP), and heart period (HP) were recorded continuously using the previously described technique (22,23). Briefly, rats were anesthetized with a combination of ketamine and diazepam.…”

Section: Bp Measurementmentioning

confidence: 99%

Arterial Baroreflex Dysfunction Fails to Mimic Parkinson’s Disease in Rats

Shen

et al. 2008

J Pharmacol Sci

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Abstract. Patients with Parkinson's disease (PD) often have attenuated baroreflex function, which may occur before the onset of PD-associated movement disorders. The aim of the present study was to test whether impaired arterial baroreflex (ABR) function could contribute to the pathogenesis of PD. 6-Hydroxydopamine (8 μg in 4 μl) was microinjected into the left substantia nigra of rats to establish unilateral PD models, and bilateral PD models were established in rats by administration of rotenone by osmotic minipump for four weeks, at a dose of 2.5 mg ⋅ kg −1 ⋅ day −1 . An ABR dysfunction model was obtained by performing sinoaortic denervation (SAD). Hemodynamic variables were determined in conscious rats. PD-like symptoms and dopamine content in corpus striatum (CS) were also assessed. 6-Hydroxydopamine and rotenone treatment and SAD were associated with enhanced blood pressure variability (BPV) and blunted baroreflex sensitivity (BRS). Rotenone, but not SAD, significantly reduced dopamine content in the CS, induced catalepsy, and inhibited rearing and exploratory behavior. SAD before the administration of rotenone did not aggravate the rotenone-induced dopaminergic lesion. Our findings do not support the presumption that ABR dysfunction contributes to the pathogenesis of PD in rats.

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Section: Bp Measurementmentioning

confidence: 99%

Arterial Baroreflex Dysfunction Fails to Mimic Parkinson’s Disease in Rats

Shen

et al. 2008

J Pharmacol Sci

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“…11 Previously, SAD rats have been used for the study of acute and chronic effects of antihypertensive drugs on BPV and target organ damage. [12][13][14][15] Nevertheless, to the best our knowledge, effects of third generation b-blockers on short-term fluctuations of blood pressure have not been studied in this experimental model. Therefore, the aim of the present work was to compare the effects of atenolol (a second generation b-blocker), carvedilol (a third generation b-blocker), nebivolol (a third generation b-blocker) and verapamil (a calcium channel blocker) on blood pressure and shortterm BPV in SAD rats.…”

Section: Introductionmentioning

confidence: 99%

Acute effects of third generation β-blockers on short-term and beat-to-beat blood pressure variability in sinoaortic-denervated rats

et al. 2013

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An increase in blood pressure variability (BPV) contributes to the development of target organ damage associated with hypertension. Treatment with conventional β-blockers, such as atenolol, has been associated with an increase in BPV; however, the extrapolation of these results to third generation β-blockers with pleiotropic effects seems to be inappropriate. The cardiovascular effects of third generation β-blockers, carvedilol and nebivolol, were assessed in sinoaortic-denervated rats (SAD) and compared with the second generation β-blocker atenolol and the calcium channel blocker verapamil, with a special focus on short-term BPV. Male SAD rats were acutely treated with carvedilol, nebivolol, atenolol or verapamil at two different doses, and the effects on blood pressure and BPV were recorded. Short-term BPV was assessed by the s.d. of BP recordings. Beat-to-beat BPV was studied using spectral analysis to assess the vascular sympatholytic activity of carvedilol and nebivolol by estimating the effects of these drugs on the ratio of low frequency (LF) to high frequency (HF) BPV (LF/HF ratio). Nebivolol, carvedilol and the calcium channel blocker verapamil significantly attenuated short-term BPV at both doses in SAD animals, and there were no differences between the drugs. Conversely, atenolol did not modify baseline s.d. values at either dose. Carvedilol and nebivolol significantly reduced the LF/HF ratio in SAD rats compared with the effects of atenolol and verapamil, suggesting the ability of the third generation β-blockers to reduce vascular sympathetic activity. In conclusion, third generation β-blockers induce a marked reduction in short-term BPV in SAD rats compared to atenolol. Moreover, the ability of carvedilol and nebivolol to reduce short-term BPV in SAD rats is equivalent to that of verapamil, suggesting that these β-blockers may have an additional beneficial effect through their control of short-term variability to a similar extent to calcium channel blockers.

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“…administration of nifedipine induce BP decrease in SHR, which is accompanied by a sustained elevation of the HR [48,49]. and p.o.…”

Section: Discussionmentioning

confidence: 96%

“…and p.o. administration of nifedipine induce BP decrease in SHR, which is accompanied by a sustained elevation of the HR [48,49]. In both normotensive rats and SHR, nicardipine administered either as a bolus injection or orally decreases BP and increases HR [50].…”

Section: Discussionmentioning

confidence: 99%

Vasodilator and antihypertensive effects of a novel N‐acylhydrazone derivative mediated by the inhibition of L‐type Ca²⁺ channels

Pereira

Kümmerle

Fraga

et al. 2012

Fundamemntal Clinical Pharma

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New bioactive N-acylhydrazone derivatives synthesized from safrole previously have been found to promote intense vasodilation and antihypertensive activity. In this study, we describe the synthesis and the cardiovascular effects of the new N-acylhydrazone derivative (E)-N-methyl-N'-(thiophen-3-ylmethylene)benzo[d][1,3]dioxole-5-carbohydrazide (LASSBio-1289). Thoracic aorta and left papillary muscles from Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHR) were prepared for isometric tension recording. LASSBio-1289 promoted relaxation of endothelium-intact and denuded aortic rings with respective pIC₅₀ (-log IC₅₀) values of 5.07 ± 0.09 and 4.26 ± 0.09 (P < 0.001) for WKY rats and 5.43 ± 0.05 and 5.58 ± 0.07 (P > 0.05) for SHR. The vasodilator activity of LASSBio-1289 was increased in the KCl-contracted aorta. LASSBio-1289 attenuated the contracture elicited by Ca(2+) in depolarized aorta from both WKY rats and SHR. In endothelium-intact aorta from WKY rats, LASSBio-1289-induced relaxation was unchanged after incubation with propranolol, ZM 241385, atropine, diphenhydramine, and HOE140, but was significantly reduced by L-NAME and ODQ. LASSBio-1289 decreased papillary muscles contractility only at concentrations above 200 μm. Acute intravenous injection of LASSBio-1289 (3 mg/kg) produced a significant hypotensive response in SHR but not in WKY rats, suggesting its antihypertensive profile. The antihypertensive effect was also observed in SHR during 14 days of intraperitoneal and oral administration. In conclusion, our data demonstrated that LASSBio-1289 induces both endothelium-independent vasorelaxation involving the inhibition of Ca(2+) influx through L-type Ca(2+) channels in aorta from WKY rats and SHR, and endothelium-dependent relaxation mediated by the NO/cyclic GMP pathway in WKY rats.

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Functional Arterial Baroreflex Attenuates the Effects of Antihypertensive Drugs in Conscious Rats

Cited by 4 publications

References 22 publications

Arterial Baroreflex Dysfunction Fails to Mimic Parkinson’s Disease in Rats

Arterial Baroreflex Dysfunction Fails to Mimic Parkinson’s Disease in Rats

Acute effects of third generation β-blockers on short-term and beat-to-beat blood pressure variability in sinoaortic-denervated rats

Vasodilator and antihypertensive effects of a novel N‐acylhydrazone derivative mediated by the inhibition of L‐type Ca²⁺ channels

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Functional Arterial Baroreflex Attenuates the Effects of Antihypertensive Drugs in Conscious Rats

Cited by 4 publications

References 22 publications

Arterial Baroreflex Dysfunction Fails to Mimic Parkinson’s Disease in Rats

Arterial Baroreflex Dysfunction Fails to Mimic Parkinson’s Disease in Rats

Acute effects of third generation β-blockers on short-term and beat-to-beat blood pressure variability in sinoaortic-denervated rats

Vasodilator and antihypertensive effects of a novel N‐acylhydrazone derivative mediated by the inhibition of L‐type Ca2+ channels

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Vasodilator and antihypertensive effects of a novel N‐acylhydrazone derivative mediated by the inhibition of L‐type Ca²⁺ channels