Effects of 4-week administration of simvastatin in different doses on heart rate and blood pressure after metoprolol injection in normocholesterolaemic and normotensive rats

Owczarek, Jacek; Jasińska, Magdalena; Wejman, I; Kurczewska, Urszula; Orszulak–Michalak, Daria

doi:10.5114/aoms.2012.27275

Cited by 8 publications

(9 citation statements)

References 19 publications

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“…Taking into consideration the increase in HTN prevalence and the complex pathogenesis mechanism, targeting inflammation as a possible antihypertensive therapy is a new option. Evidence showed that several cardiovascular drugs like statins, ACEI, ARBs, and calcium channel blockers lowered blood pressure and serum inflammatory cytokines concentrations [54, 162, 164, 167, 171–179]. Even if antihypertensive effects of monoclonal antibodies remain controversial, some experimental animal studies showed that IL-6 inhibition in hypertensive specimens decreased myocardial fibrosis and reduced albuminuria, emphasizing the role of the proinflammatory cytokine in developing end-organ damage [180].…”

Section: Discussionmentioning

confidence: 99%

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Arterial Hypertension and Interleukins: Potential Therapeutic Target or Future Diagnostic Marker?

Tănase

Gosav

Radu³

et al. 2019

International Journal of Hypertension

109

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Hypertension as a multifactorial pathology is one of the most important cardiovascular risk factors, affecting up to 30-40% of the general population. Complex immune responses are involved in the inflammatory mechanism of hypertension, with evidence pointing to increased inflammatory mediators even in prehypertensive patients. Increased vascular permeability, thrombogenesis, and fibrosis, effects that are associated with sustained hypertension, could be attributed to chronic inflammation. Chronic inflammation triggers endothelial dysfunction via increased production of ROS through proinflammatory cytokines. Increased serum level of proinflammatory cytokines such as IL-1β, IL-6, IL-8, IL-17, IL-23, TGFβ, and TNFα in hypertensive patients has been associated with either increased blood pressure values and/or end-organ damage. Moreover, some cytokines (i.e., IL-6) seem to determine a hypertensive response to angiotensin II, regardless of blood pressure values. Understanding hypertension as an inflammatory-based pathology gives way to new therapeutic targets. As such, conventional cardiovascular drugs (statins, calcium channels blockers, and ACEIs/ARBs) have shown additional anti-inflammatory effects that could be linked to their blood pressure lowering properties. Moreover, anti-inflammatory drugs (mycophenolate mofetil) have been shown to decrease blood pressure in hypertensive patients or prevent its development in normotensive individuals. Further research is needed to evaluate whether drugs targeting hypertensive-linked proinflammatory cytokines, such as monoclonal antibodies, could become a new therapeutic option in treating arterial hypertension.

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Section: Discussionmentioning

confidence: 99%

“…Hypertensive patients tend to have increased interleukin 1 β secretion under Ang II stimulation compared to normotensive individuals. Simvastatin therapy reduced Il-1 β levels independently of lipid-lowering effects [167].…”

Section: Inflammation As a Potential Therapeutic Target In Arteriamentioning

confidence: 99%

Arterial Hypertension and Interleukins: Potential Therapeutic Target or Future Diagnostic Marker?

Tănase

Gosav

Radu³

et al. 2019

International Journal of Hypertension

109

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“…21,22 The effect of statins on BP have been studied in a number of clinical trials which, however, provided conflicting results. 23–31 Studies on the potential hypotensive effect of statins have also provided conflicting results. 27–31…”

Section: Discussionmentioning

confidence: 99%

Effects of combined statin and ACE inhibitor therapy on endothelial function and blood pressure in essential hypertension - a randomised double-blind, placebo controlled crossover study

Ruszkowski

Masajtis-Zagajewska

Nowicki

2019

J Renin Angiotensin Aldosterone Syst

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Background: The aim of this study was to compare the influence of 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors on endothelial function and blood pressure in patients with essential hypertension on long-term angiotensin-converting enzyme inhibitor therapy. Method: The study was designed as a prospective, double-blind, randomised, placebo controlled, crossover clinical trial. Twenty patients with essential hypertension were treated with an angiotensin-converting enzyme inhibitor; the control group included 10 healthy subjects. Hypertensive patients received in random order 80 mg of fluvastatin daily or placebo for 6 weeks. The following parameters were assessed at baseline and after each treatment period: serum lipids, flow-mediated vasodilation, activity of von Willebrand factor, concentration of vascular endothelial growth factor, C-reactive protein and 24-hour blood pressure profile. Results: Hypertensive patients did not differ from healthy subjects with respect to age, body mass and biochemical parameters, with the exception of C-reactive protein, which was higher in hypertensive patients ( P=0.02). After statin therapy, low-density lipoprotein cholesterol ( P<0.0001), C-reactive protein ( P=0.03), von Willebrand factor ( P=0.03) and vascular endothelial growth factor ( P<0.01) decreased and flow-mediated vasodilation improved ( P<0.001). Statins had no significant effect on blood pressure. Conclusions: Statins added to angiotensin-converting enzyme inhibitors may improve endothelial function and ameliorate inflammation independently of blood pressure.

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“…It has been found that simvastatin or pravastatin did not enhance the blood pressure–lowering action of angiotensin‐converting enzyme inhibitors, AT 1 receptor blockers, calcium channel blockers, or beta blockers .…”

Section: Discussionmentioning

confidence: 99%

“…However, the results regarding blood pressure-lowering effect of statins are conflicting [14][15][16][17][18].…”

Section: Introductionmentioning

confidence: 99%

Effect of simvastatin on the antihypertensive activity of losartan in hypertensive hypercholesterolemic animals and patients: Role of nitric oxide, oxidative stress, and high‐sensitivity C‐reactive protein

Abdel-Zaher

Elkoussi

Abudahab

et al. 2013

Fundamemntal Clinical Pharma

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This study investigated whether simvastatin has antihypertensive activity and can enhance the antihypertensive effect of losartan in hypertensive hypercholesterolemic animals and patients. Hypertension and hypercholesterolemia were induced in rats by L-NAME and cholesterol-enriched diet, respectively. In these animals, repeated administration of simvastatin decreased the systolic blood pressure, enhanced its progressive reductions induced by repeated administration of losartan, and corrected the compromised lipid profile. Concomitantly, repeated administration of simvastatin, losartan, or simvastatin in combination with losartan to these animals increased nitric oxide (NO) production and decreased the elevated serum malondialdehyde (MDA) and high-sensitivity C-reactive protein (hs-CRP) levels. Effects of combined treatment were greater than those of simvastatin or losartan alone. In hypertensive hypercholesterolemic patients, repeated administration of losartan decreased systolic and diastolic blood pressure, increased NO production, and decreased the elevated serum MDA and hs-CRP levels. Addition of simvastatin to losartan therapy enhanced these effects and corrected the compromised lipid profile. Simvastatin inhibited the contractile responses of isolated aortic rings induced by angiotensin II and enhanced the inhibitory effect of losartan on this preparation. l-arginine and acetylcholine enhanced, while L-NAME inhibited the effects of simvastatin, losartan, and their combination on these contractile responses. Thus, simvastatin exerts antihypertensive effect in hypertensive hypercholesterolemic animals and enhances the antihypertensive effect of losartan in hypertensive hypercholesterolemic animals and patients. Besides, its cholesterol-lowering effect, the ability of simvastatin to ameliorate endothelial dysfunction through increasing NO bioavailability and through suppression of oxidative stress and vascular inflammation may play an important role in these effects.

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Effects of 4-week administration of simvastatin in different doses on heart rate and blood pressure after metoprolol injection in normocholesterolaemic and normotensive rats

Cited by 8 publications

References 19 publications

Arterial Hypertension and Interleukins: Potential Therapeutic Target or Future Diagnostic Marker?

Arterial Hypertension and Interleukins: Potential Therapeutic Target or Future Diagnostic Marker?

Effects of combined statin and ACE inhibitor therapy on endothelial function and blood pressure in essential hypertension - a randomised double-blind, placebo controlled crossover study

Effect of simvastatin on the antihypertensive activity of losartan in hypertensive hypercholesterolemic animals and patients: Role of nitric oxide, oxidative stress, and high‐sensitivity C‐reactive protein

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