Effect of beta-1-blocker, nebivolol, on central aortic pressure and arterial stiffness in patients with essential hypertension

Year : 2012  |  Volume : 44  |  Issue : 3  |  Page : 407-411

Indian J Pharmacol. Radhika Soanker1, M.U.R Naidu1, Sree Bhushan Raju2, A Krishna Prasad3, T Ramesh Kumar Rao1 1 Department of Clinical Pharmacology and Therapeutics, Nizams Institute of Medical Sciences, Hyderabad, India 2 Department of Nephrology, Nizams Institute of Medical Sciences, Hyderabad, India 3 Department of General Medicine, Nizams Institute of Medical Sciences, Hyderabad, India

Introduction

Blood pressure (BP) reduction is the major determinant of benefit provided by antihypertensive treatment. Although different drugs reduce peripheral BP to some extent, there may be a significant difference in their effect on central BP reduction. It has been shown that beta-blockers are efficient in reducing peripheral, but not central BP. This study was done to assess the effect of beta-1-blocker, nebivolol, in patients with essential hypertension on central aortic pressures and arterial stiffness.

Materials and Methods

In this single arm, open-labeled study, 13 patients were given nebivolol, 5 mg orally once daily for 15 days. Primary outcome was change in central aortic pressure, and other measures of efficacy included changes in brachial BP, augmentation index (AIx%), AIx%@75 HR, augmentation pressure (AP), heart rate (HR), and carotid femoral pulse wave velocity (PWVcf).

Results

Nebivolol 5 mg significantly reduced central aortic pressures [systolic BP, 131.5-111.6 mmHg; diastolic BP, 96.3-81.7 mmHg; Mean Arterial Pressure (MAP), 111.3-94.0 mmHg (all P<0.0001), and Pulse Pressure (PP), 35.2-29.7 mmHg (P<0.01)]. AIx%@75 HR reduced from 29 to 21.6 (P<0.001) and PWVcf reduced from 8.6 to 7.2 m/s (P<0.001). One subject was lost to followup.

Conclusion 

Nebivolol 5 mg demonstrated antihypertensive efficacy in patients with essential hypertension by reducing not only peripheral brachial pressures, but also significantly reducing central aortic pressures, augmentation index, and carotid femoral pulse wave velocity, which is the marker of arterial stiffness.

Keywords: Nebivolol, central aortic pressures, arterial stiffness

*In Pakistan, it is marketed by Searle Pakistan Limited as Byscard.

                                                                                      

Seminar on the latest approach for controlling Blood Pressure

         

Searle Pakistan Limited has organized a Seminar on the latest approach for controlling Blood Pressure, his topic of presentation was “Vasodilating Beta-Blockers The New Frontier” at a local hotel in Karachi; it was one of the seminars of Continuous Medical Education (CME) program of the organization for increasing scientific awareness among the medical community for better patient management.

Prof. Azhar Masood Farooqi, an icon in the field of Cardiology and Former Executive Director, National Institute of Cardiovascular Diseases was the chief guest at the occasion while Prof. Khan Shah Zaman, Executive Director, National Institute of Cardiovascular Diseases was the chair of the seminar and Prof. M. Z. Jilani Consultant Physician & Cardiologist, Ziauddin Medical University Karachi was the key speaker of the seminar. More than 150 Doctors participated in the interactive session from different institutes and areas of Karachi in that CME activity.

The program was started with the recitation of Holy Quran and I commenced the session as moderator and formally introduced and invited guests on stage to chair the Seminar.

While introducing the academicians, I shared the success story of Searle Pakistan Limited to become among the top ten companies of Pakistan and known among the healthcare community because of its quality products, efficacy and affordable price.

Formally seminar was commenced with a short speech of Deputy Managing Director Mr. Hassan Tariq, he shared briefly about the services of Searle Pakistan for the people of Pakistan and shares the concept of “Business with social responsibility”. He assured the participants that Searle will provide quality Products for healthcare community to overcome the misery of ailing humanity. He thanked Prof. Azhar Masood Farooqi, an icon in the field of Cardiology as a chief guest, Prof. Khan Shah Zaman, Executive Director, National Institute of Cardiovascular Diseases and Prof. M. Z. Jilani Consultant Physician & Cardiologist, Ziauddin Medical University for their precious time for Byscard seminar, and also thanked participants for their kind efforts and trust which they conferred on Searle Pakistan.

Now Prof. M. Z. Jilani invited for his presentation on Hypertension, in which he discussed the prevalence and global cardiovascular disease mortality and incidence of Hypertension in America, Europe and third world countries and finally in Pakistan. Secondly he shared the stages of hypertension, cardiovascular disease risk factors and consequences of Hypertension in end organ damage with their dangerous outcomes.

Nebivolol is the 3^rd Generation new innovative Cardio-selective β-Blocker which provides even better Blood Pressure reduction in comparison with all other conventional β-blockers without β-Blocker like side effects.’ 

• Nebivolol Approved by FDA and ESC in hypertension and heart failure.
• Nebivolol has unique mode of action.
• Nebivolol has the highest B₁-receptor affinity among Beta-blockers and has potent vasodilatory effects to improve endothelial function.
• Nebivolol once daily treatment significantly reduces systolic and diastolic blood pressure in patients.
• Nebivolol Provides improvement in erectile function in hypertensive patients compared with other B-blockers.
• Nebivolol Well tolerated with proven efficacy in heart failure.
• Reduction in all cause mortality/CV hospitalization.
• Nebivolol can lead to 1/3 reduction in the risk of ischemic events.

Prof. Azhar Masood Farooqi and Prof. Khan Shah Zaman concluded the session with the remarks that Nebivolol is remarkable and safest option in order to treat the cardiovascular disorders. He emphasized on doctors to use effective drug therapy to minimize the fatal risks and to enhance the quality of patients’ life.

Effect of beta-1-blocker, nebivolol, on central aortic pressure and arterial stiffness in patients with essential hypertension
Indian J Pharmacol. Year : 2012  |  Volume : 44  |  Issue : 3  |  Page : 407-411

Introduction

Blood pressure (BP) reduction is the major determinant of benefit provided by antihypertensive treatment. Although different drugs reduce peripheral BP to some extent, there may be a significant difference in their effect on central BP reduction. It has been shown that beta-blockers are efficient in reducing peripheral, but not central BP. This study was done to assess the effect of beta-1-blocker, nebivolol, in patients with essential hypertension on central aortic pressures and arterial stiffness.

Materials and Methods

In this single arm, open-labeled study, patients were given nebivolol, 5 mg orally once daily for 15 days. Primary outcome was change in central aortic pressure, and other measures of efficacy included changes in brachial BP, augmentation index (AIx%), AIx%@75 HR, augmentation pressure (AP), heart rate (HR), and carotid femoral pulse wave velocity (PWVcf).

Results

Nebivolol 5 mg significantly reduced central aortic pressures [systolic BP, 131.5-111.6 mmHg; diastolic BP, 96.3-81.7 mmHg; Mean Arterial Pressure (MAP), 111.3-94.0 mmHg (all P<0.0001), and Pulse Pressure (PP), 35.2-29.7 mmHg (P<0.01)]. AIx%@75 HR reduced from 29 to 21.6 (P<0.001) and PWVcf reduced from 8.6 to 7.2 m/s (P<0.001). One subject was lost to followup.

Conclusion

Nebivolol 5 mg demonstrated antihypertensive efficacy in patients with essential hypertension by reducing not only peripheral brachial pressures, but also significantly reducing central aortic pressures, augmentation index, and carotid femoral pulse wave velocity, which is the marker of arterial stiffness.

*In Pakistan, it is marketed by Searle Pakistan Limited as Byscard.

The Treatment of Hypertensive Asthmatic Subjects with Highly Selective β blocker - Nebivolol

Abstract 

Rationale

The benefit from using selective β blockers due to arterial hypertension and ischemic heart disease is well known. Asthmatic subjects are the special “group of risk” with relative contraindications for this therapy. The novel highly selective β-blocker nebivolol which additionally posses vasodilatatory effect through nitric oxide release is potentially safe in asthma.

Methods

The aim of the study was to evaluate the influence of one dose 5 mg of nebivolol orally administrated compared with placebo to spirometric parameters and blood pressure. The study was performed double-blind cross–over method in patient with mild/moderate persistent asthma. The patients were treated with nebivolol or placebo with 7 days of “wash–out”. The spirometry was done at 0, 2 h, 6h and 24 h after administration. Blood pressure was measured continuously through 24 hours.

Results

None of the patient reacted with dyspnoe or with significant fall of FEV₁. In all cases a moderate but significant decrease of blood pressure was observed.

Conclusions

Nebivolol seems to be a safe and effective in treatment asthmatic hypertensive patients.

*In Pakistan, it is marketed by Searle Pakistan Limited as Byscard.

NITRIC OXIDE, ERECTILE DYSFUNCTION AND BETA-BLOCKER TREATMENT (MR NOED STUDY): BENEFIT OF NEBIVOLOL VERSUS METOPROLOL IN HYPERTENSIVE MEN

Hypertensive men treated with beta-blockers frequently complain of erectile dysfunction. The present study investigated the effects of two b1-adrenoceptor-selective antagonists, namely nebivolol and metoprolol, on erectile function in hypertensive men.

Metoprolol, but not nebivolol, significantly decreased the IIEF erectile function subscore by 0.92 in the first 8 weeks after onset of beta-blocker treatment. In contrast with metoprolol, nebivolol improved secondary sexual activity scores and other IIEF subscores.

Nebivolol may improve erectile function by increasing perfusion in small and microvessels. Similar effects have been described for sildenafil, a phosphodiesterarse 5 inhibitor.

Nebivolol may offer additional benefits by avoiding erectile dysfunction in male hypertensive patients on long-term b- adrenoceptor antagonist therapy.

Reference:

Clinical and Experimental Pharmacology and Physiology (2007) 34, 327–331

In Pakistan, it is marketed by Searle Pakistan Limited as Byscard.

Nebivolol Dilates Human Penile Arteries and Reverses Erectile Dysfunction

Introduction

Traditional beta-blockers have sometimes been associated with erectile dysfunction (ED). Nebivolol is a cardioselective β₁-adrenoceptor antagonist that promotes vasodilation through a nitric oxide (NO)-dependent mechanism.

Aim

We evaluated the effects of nebivolol on the NO/cyclic guanosine monophosphate (cGMP) signaling pathway, on erectile function and dysfunction, and in human penile vascular tissues.

Methods

Erectile response to cavernosal nerve electrical stimulation in control and diabetes-induced ED rats were evaluated, along with serum nitrite/nitrate (NOx) concentration and plasma/tissue cGMP levels. Endothelium-dependent and sildenafil-induced relaxation of isolated human corpus cavernosum (HCC) and human penile resistance arteries (HPRA) were also determined.
Main Outcome Measures

The effects of nebivolol on erectile function and dysfunction and on NO/cGMP-mediated responses.
Results

Treatment with nebivolol significantly potentiated erectile response in control rats, regardless of its effects on blood pressure. Nebivolol increased NOx and plasma cGMP by 3-fold and 2.75-fold, respectively, and significantly augmented the elevation of plasma cGMP produced by sildenafil. Nebivolol enhanced endothelium-dependent and sildenafil-induced relaxations of HCC tissue, and produced endothelium-dependent vasodilation of HPRA. Nebivolol, but not atenolol, significantly improved erectile response in diabetic rats (51.6%, 53.2%, and 87.1% of response at 3 Hz in nondiabetic rats, for vehicle-treated, atenolol-treated, and nebivolol-treated diabetic rats, respectively); after sildenafil administration, ED was completely reversed in nebivolol-treated diabetic rats (69.6% and 112% for diabetic rats treated with sildenafil and nebivolol plus sildenafil, respectively). Accordingly, nebivolol restored systemic NOx levels and cGMP content in penile tissue from these animals.
Conclusions

Nebivolol in vivo activated the NO/cGMP pathway, enhanced erectile response and reversed ED in diabetic rats. Moreover, nebivolol in vitro potentiated NO/cGMP-mediated relaxation of human erectile tissues. These effects may account for the low incidence of ED in nebivolol-treated hypertensive patients. Nebivolol therefore may have utility in the treatment of ED, particularly ED associated with diabetes.

Reference:

Angulo J, Wright HM, Cuevas P, González-Corrochano R, Fernández A, Cuevas B, La Fuente JM, Gupta S, and de Tejada IS. Nebivolol dilates human penile arteries and reverses erectile dysfunction in diabetic rats through enhancement of nitric oxide signaling. J Sex Med 2010;7:2681–2697.

In Pakistan, it is marketed by Searle Pakistan Limited as Byscard.

Pulmonary Effects of Nebivolol

The pharmacological control of arterial hypertension is a very frequent issue in clinical practice and some critical aspects can arise in particular circumstances and with particular molecules. In the case of hypertensive subjects with respiratory comorbidities, when first introduced, these β-adrenergic receptor antagonists were described as affecting airway patency as a result of their antagonism against β₂-adrenergic receptors within airway muscles. New molecules with a better respiratory tolerability were subsequently designed in order to overcome the narrow therapeutic window of first-generation β-adrenergic receptor antagonists. Nebivolol is a third-generation β-adrenergic receptor antagonist with high β₁-selective adrenergic receptor antagonism and vasodilating properties that induces a substantial decrease of arterial pressure in hypertensive subjects while preserving their left ventricular function. Respiratory effects of nebivolol have been investigated in animal models, in healthy volunteers and in clinical trials carried out on patients suffering from bronchial asthma and chronic obstructive pulmonary disease (COPD). In contrast to older compounds, nebivolol, which modulates the endogenous production of nitric oxide and affects oxidative cascade, proved clinically well tolerated in terms of respiratory outcomes in this type of subject. Moreover, due to the substantial dissociation between its cardiac and pulmonary activity, nebivolol confirmed a very good safety profile when regularly administered to hypertensive subjects with obstructive respiratory comorbidities.

In Pakistan, it is marketed by Searle Pakistan Limited as Byscard.