Effect of nebivolol on beat-to-beat and short-term blood pressure variability in spontaneously hypertensive rats

Bertera, Facundo M.; Mauro, Julieta S. Del; Polizio, Ariel Héctor; Taira, Carlos A.; Höcht, Christián

doi:10.1007/s00210-012-0756-9

Cited by 13 publications

(16 citation statements)

References 42 publications

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“…We have demonstrated that nebivolol at doses of 0.3 and 3 mg/kg did not modify mean arterial pressure in normotensive conscious rats [27]. However, dual combination between tempol and nebivolol i.v administration at a dose of 3 mg/kg produces a drop in MAP without affecting HR substantially between the C, T, CN and TN groups.…”

Section: Discussionmentioning

confidence: 79%

Tempol-nebivolol therapy potentiates hypotensive effect increasing NO bioavailability and signaling pathway

Bertera

Santa-Cruz

Balestrasse

et al. 2013

Free Radical Research

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Nebivolol is a third generation beta blocker with endothelial nitric oxide synthase (eNOS) agonist properties. Considering the role of reactive oxygen species (ROS) in the uncoupling of eNOS, we hypothesized that the preadministration of an antioxidant as tempol, could improve the hypotensive response of nebivolol in normotensive animals increasing the nitric oxide (NO) bioavailability by a reduction of superoxide (O 2 .-) basal level production in the vascular tissue. Male Sprague Dawley rats were given tap water to drink (control group) or tempol (an antioxidant scavenger of superoxide) for 1 week. After 1 week, Nebivolol, at a dose of 3 mg/kg was injected intravenously to the control group or tempol treated group. Mean arterial pressure, heart rate and blood pressure variability were evaluated in the control, tempol, nebivolol and tempol nebivolol groups, as well as, the effect of different inhibitor as N W -nitro-l-arginine methyl ester (L-NAME, a Nitric oxide synthase blocker) or glybenclamide, a K ATP channel inhibitor. Also, the expression of α,β soluble guanylate cyclase (sGC), phospho-eNOS, and phosphovasodilator-stimulated phosphoprotein (P-VASP) were evaluated by Western Blot and cyclic guanosine monophosphate (cGMP) levels by an enzyme-linked immunosorbent assay (ELISA) commercial kit assay.We showed that preteatment with tempol in normotensive rats produces a hypotensive response after nebivolol administration through an increase in the NO bioavailability and sGC, improving the NO/ cGMP/ protein kinase G (PKG) pathway compared to the nebivolol group.We demonstrated that tempol preadministration beneficiates the response of a third generation beta blocker with eNOS stimulation properties, decreasing the basal uncoupling of eNOS and improving NO bioavailability. Our results clearly open a possible new strategy therapeutic for treating hypertension.Free Radic Res Downloaded from informahealthcare.com by Loyola University on 10/05/13For personal use only. For personal use only. J U S T A C C E P T E D J U S T A C C E P T E D AbstractNebivolol is a third generation beta blocker with endothelial nitric oxide synthase (eNOS) agonist properties. Considering the role of reactive oxygen species (ROS) in the uncoupling of eNOS, we hypothesized that the preadministration of an antioxidant as tempol, could improve the hypotensive response of nebivolol in normotensive animals increasing the nitric oxide (NO) bioavailability by a reduction of superoxide (O 2 .-) basal level production in the vascular tissue.Male Sprague Dawley rats were given tap water to drink (control group) or tempol (an antioxidant scavenger of superoxide) for 1 week. After 1 week, Nebivolol, at a dose of 3 mg/kg was injected intravenously to the control group or tempol treated group. Mean arterial pressure, heart rate and blood pressure variability were evaluated in the control, tempol, nebivolol and tempol nebivolol groups, as well as, the effect of different inhibitor as N W -nitro-l-arginine methyl ester (L-NAME, a Nitric oxide...

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Section: Discussionmentioning

confidence: 79%

Tempol-nebivolol therapy potentiates hypotensive effect increasing NO bioavailability and signaling pathway

Bertera

Santa-Cruz

Balestrasse

et al. 2013

Free Radical Research

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“…An interesting finding of this set of experiments is the fact that nebivolol markedly attenuates short-term BPV in spontaneously hypertensive rats and normotensive animals and this beneficial effect is evident at low dose levels associated with limited effects on mean BP values (Figure 2) [69].…”

Section: Preclinical Evidencementioning

confidence: 78%

“…Acute intravenous administration of a single dose of third-generation beta blockers, carvedilol, and nebivolol, also effectively controls short-term BPV in freely moving spontaneously hypertensive rats and normotensive control animals [14,69]. An interesting finding of this set of experiments is the fact that nebivolol markedly attenuates short-term BPV in spontaneously hypertensive rats and normotensive animals and this beneficial effect is evident at low dose levels associated with limited effects on mean BP values (Figure 2) [69].…”

Section: Preclinical Evidencementioning

confidence: 81%

Blood Pressure Variability: Prognostic Value and Therapeutic Implications

Höcht

2013

ISRN Hypertension

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Blood pressure variability (BPV) is considered nowadays a novel risk factor for cardiovascular disease. Early findings in sinoaortic denervated rats have clearly shown that enhanced fluctuation of blood pressure induced left ventricular hypertrophy, vascular stiffness, and renal lesion. A large number of clinical trials confirm that short-term and long-term blood pressure variability independently contributes to target organ damage, cardiovascular events, and mortality not only in hypertensive patients but also in subjects with diabetes mellitus and chronic kidney disease. Therefore, amelioration of BPV has been suggested as an additional target of the treatment of cardiovascular diseases. Preliminary evidence obtained from meta-analysis and controlled clinical trials has shown that antihypertensive classes differ in their ability to control excessive BP fluctuations with an impact in the prevention of cardiovascular events. Calcium channel blockers seem to be more effective than other blood pressure lowering drugs for the reduction of short-term and long-term BPV. In order to increase actual knowledge regarding the prognostic value and therapeutic significance of BPV in cardiovascular disease, there is a need for additional clinical studies specifically designed for the study of the relevance of short-term and long-term BPV control by antihypertensive drugs.

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“…Bizonyították, hogy a 3. generációs béta-blokkoló carvedilol és nebivolol egyszeri iv. dózissal hatásosan csökkenti a BPV-t hypertoniás patkányokban és normotoniás egyedekben egyaránt, elsősorban nagyobb dózisok alkalmazásakor [13,14,38].…”

Section: Experimentális Vizsgálatokunclassified

Measurement of blood pressure variability and the clinical value

Kékes

Kiss

2014

Orvosi Hetilap

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A szerzők összefoglalják és elemzik a vérnyomás-variabilitásról szóló irodalmi adatokat. Bemutatják a vérnyomás-variabilitás mérési típusait, azok klinikai értékét, összefüggésüket a szervi károsodásokkal és a cardiovascularis esemé-nyek megjelenésének kockázatával. Jellemzik a prognosztikai értékre vonatkozó adatokat és áttekintik a különböző antihipertenzív szereknek a vérnyomás-variabilitásra kifejtett hatásait. Véleményük szerint ma már bizonyítottnak tekinthető, hogy a hypertonia kezelése során a vérnyomáscélérték elérése mellett törekedni kell a vérnyomás-variabilitás csökkentésére, a vérnyomás-fl uktuáció befolyásolására, mert ez jelenti az egyik legnagyobb veszélyt a hypertoniás egyén számára. Beszámolnak a hazai tapasztalatokról is. Reményteljesnek tartják, hogy a nemzetközi irányelvekben a vérnyomás-variabilitás mérése teret nyert. Orv. Hetil., 2014, 155(42), 1661-1672. Kulcsszavak: vérnyomás-variabilitás, vérnyomás-fl uktuáció, vérnyomás-variabilitás és szervi károsodások, vérnyo-más-variabilitás és hypertoniaprognózis, antihipertenzív gyógyszerhatás Measurement of blood pressure variability and the clinical valueAuthors have collected and analyzed literature data on blood pressure variability. They present the methods of blood pressure variability measurement, clinical value and relationships with target organ damages and risk of presence of cardiovascular events. They collect data about the prognostic value of blood pressure variability and the effects of different antihypertensive drugs on blood pressure variability. They underline that in addition to reduction of blood pressure to target value, it is essential to infl uence blood pressure fl uctuation and decrease blood pressure variability, because blood pressure fl uctuation presents a major threat for the hypertensive subjects. Data from national studies are also presented. They welcome that measurement of blood pressure variability has been included in international guidelines.Keywords: blood pressure variability, blood pressure fl uctuation, blood pressure variability and target organ damage, blood pressure variability and prognosis, effects of antihypertensive drugs Rövidítések ABPM = 24 órás vérnyomás-monitorozás; ACE = angiotenzinkonvertáló enzim; ARV = átlagos reális variabilitás; BP = vér-nyomás; BPV = vérnyomás-variabilitás; CAA = kalciumantagonista; CV = cardiovascularis; DBP = diasztolés vérnyomás; DBPV= diasztolés vérnyomás variabilitása; DM2T = 2-es típu-sú diabetes mellitus; ESC = European Society of Cardiology; ESH = European Society of Hypertension; GFR = glomerulusfi ltrációs ráta; HBPM = otthoni vérnyomásmérés; IMT = carotis intima-media vastagság; LF/HF = alacsony és magas frekvenciatartomány aránya (spectrumelemezés); LVH = balkamra-hipertrófi a; LVM = bal kamrai izommassza; NO = nitrogén-monoxid; OBPM = rendelői vérnyomásmérés; PTCA = percutan transluminalis koszorúér-tágítás; RAS = reninangio tenzin rendszer; SBP = szisztolés vérnyomás; SBPV = szisztolés vérnyomás variabilitás; SD = standard deviáció; SI = smoothness index;...

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Effect of nebivolol on beat-to-beat and short-term blood pressure variability in spontaneously hypertensive rats

Cited by 13 publications

References 42 publications

Tempol-nebivolol therapy potentiates hypotensive effect increasing NO bioavailability and signaling pathway

Tempol-nebivolol therapy potentiates hypotensive effect increasing NO bioavailability and signaling pathway

Blood Pressure Variability: Prognostic Value and Therapeutic Implications

Measurement of blood pressure variability and the clinical value

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