Nebivolol treatment improves resistant arterial function and reduces ventricular hypertrophy and angiotensin II in spontaneously hypertension rats

Abstract

Objective:

The objective of this article is to assess the effects of nebivolol on resistant vascular reactivity, ventricular hypertrophy and the renin–angiotensin system in spontaneously hypertension rats (SHR).

Methods:

Rats were divided into: SHR treated with nebivolol (8 mg/kg, i.g.)/atenolol(80 mg/kg, i.g.); SHR control group; normotensive Wistar-Kyoto (WKY) control group. Vascular responses to KCl, noradrenaline (NA), endothelin-1 (ET-1), angiotensin II (Ang II), acetylcholine (ACh) and sodium nitroprusside (SNP) were tested on the femoral and renal artery. Left ventricle weight/body weight ratio (LVW/BW) was measured. Ang II and angiotensin-converting enzyme (ACE) activity in plasma and the left ventricle were determined. Plasma renin activity (PRA) was quantified.

Results:

Systolic blood pressure was decreased after nebivolol treatment in SHR. Compared with WKY, the contractions to KCl, NA, Ang II and ET-1 were increased in SHR while the relaxation to ACh was impaired. LVW/BW was higher in SHR. Levels of Ang II and ACE activity in plasma and the left ventricle were increased in SHR, but PRA was similar in these groups. Compared with atenolol, nebivolol markedly improved resistant vascular reactivity and decreased LVW/BW and Ang II. But nebivolol had no influence on ACE activity and PRA in SHR.

Conclusion:

Nebivolol treatment improved resistant arterial reactivity and reduced left ventricular hypertrophy and Ang II in SHR.

Keywords

Nebivolol SHR femoral artery renal artery renin-angiotensin system (RAS)

Get full access to this article

View all access options for this article.

References

Schiffrin

. Reactivity of small blood vessels in hypertension: Relation with structural changes. State of the art lecture. Hypertension 1992; 19: II1–9.

Bohlen

. Localization of vascular resistance changes during hypertension. Hypertension 1986; 8: 181–183.

Rosivall

. Intrarenal renin–angiotensin system. Mol Cell Endocrinol 2009; 302: 185–192.

Lee

Paul

Bohm

. Effects of angiotensin-converting enzyme inhibitors on tissue renin-angiotensin systems. Am J Cardiol 1992; 70: 12C–19C.

Verdecchia

Angeli

Mazzotta

. The renin angiotensin system in the development of cardiovascular disease: Role of aliskiren in risk reduction. Vasc Health Risk Manag 2008; 4: 971–981.

Cockcroft

. A review of the safety and efficacy of nebivolol in the mildly hypertensive patient. Vasc Health Risk Manag 2007; 3: 909–917.

Weiss

. Nebivolol: A novel beta-blocker with nitric oxide-induced vasodilatation. Vasc Health Risk Manag 2006; 2: 303–308.

Guerrero

Voces

Ardanaz

. Long-term treatment with nebivolol improves arterial reactivity and reduces ventricular hypertrophy in spontaneously hypertensive rats. J Cardiovasc Pharmacol 2003; 42: 348–355.

Angulo

Wright

Cuevas

. 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.

10.

Altwegg

d’Uscio

Barandier

. Nebivolol induces NO-mediated relaxations of rat small mesenteric but not of large elastic arteries. J Cardiovasc Pharmacol 2000; 36: 316–320.

11.

Gorski

Campbell

. Angiotensin-converting enzyme determination in plasma during therapy with converting enzyme inhibitor: Two methods compared. Clin Chem 1991; 37: 1390–1393.

12.

Wong

Man

Vanhoutte

. Calcium-independent phospholipase A(2) plays a key role in the endothelium-dependent contractions to acetylcholine in the aorta of the spontaneously hypertensive rat. Am J Physiol Heart Circ Physiol 2010; 298: H1260–H1266.

13.

Aalkjaer

Heagerty

Petersen

. Evidence for increased media thickness, increased neuronal amine uptake, and depressed excitation—contraction coupling in isolated resistance vessels from essential hypertensives. Circ Res 1987; 61: 181–186.

14.

Izzard

Heagerty

. Hypertension and the vasculature: Arterioles and the myogenic response. J Hypertens 1995; 13: 1–4.

15.

Izzard

Bund

Heagerty

. Myogenic tone in mesenteric arteries from spontaneously hypertensive rats. Am J Physiol 1996; 270: H1–H6.

16.

Schmid-Schonbein

Zweifach

DeLano

. Microvascular tone in a skeletal muscle of spontaneously hypertensive rats. Hypertension 1987; 9: 164–171.

17.

Van Bortel

de Hoon

Kool

. Pharmacological properties of nebivolol in man. Eur J Clin Pharmacol 1997; 51: 379–384.

18.

Leung

Wong

Koon

. Transgenic mice over-expressing ET-1 in the endothelial cells develop systemic hypertension with altered vascular reactivity. PloS One 2011; 6: e26994.

19.

Uematsu

Ogawa

Tokinaga

. Sevoflurane inhibits angiotensin II-induced Rho kinase-mediated contraction of vascular smooth muscle from spontaneously hypertensive rat. J Anesth 2011; 25: 398–404.

20.

Török

Koprdová

Cebová

. Functional and structural pattern of arterial responses in hereditary hypertriglyceridemic and spontaneously hypertensive rats in early stage of experimental hypertension. Physiol Res 2006; 55 (Suppl 1): S65–S71.

21.

Hayakawa

Hirata

Suzuki

. Mechanisms for altered endothelium-dependent vasorelaxation in isolated kidneys from experimental hypertensive rats. Am J Physiol 1993; 264: H1535–H1541.

22.

Maffei

Lembo

. Nitric oxide mechanisms of nebivolol. Ther Adv Cardiovasc Dis 2009; 3: 317–327.

23.

Wang

Zhang

Liu

. The effect of nebivolol on asymmetric dimethylarginine system in spontaneously hypertension rats. Vascul Pharmacol 2011; 54: 36–43.

24.

Feng

Prieto

Navar

. Nebivolol-induced vasodilation of renal afferent arterioles involves beta3-adrenergic receptor and nitric oxide synthase activation. Am J Physiol Renal Physiol 2012; 303: F775–F782.

25.

Grundt

Meier

Grundt

. Evidence for an estradiol-agonistic action of nebivolol in spontaneously hypertensive rats. J Hypertens 2007; 25: 1001–1007.

26.

Wagenfeld

Himpel

Galambos

. Protective effects of nebivolol on oxygen free radical-induced vasoconstrictions in vitro. Med Sci Monit 2008; 14: BR109–BR112.

27.

Mason

Kubant

Jacob

. Effect of nebivolol on endothelial nitric oxide and peroxynitrite release in hypertensive animals: Role of antioxidant activity. J Cardiovasc Pharmacol 2006; 48: 862–869.

28.

Kobori

Nangaku

Navar

. The intrarenal renin-angiotensin system: From physiology to the pathobiology of hypertension and kidney disease. Pharmacol Rev 2007; 59: 251–287.

29.

Hollenberg

Fisher

Price

. Pathways for angiotensin II generation in intact human tissue: Evidence from comparative pharmacological interruption of the renin system. Hypertension 1998; 32: 387–392.

30.

Padmanabhan

Jardine

McGrath

. Angiotensin-converting enzyme-independent contraction to angiotensin I in human resistance arteries. Circulation 1999; 99: 2914–2920.

31.

Linz

Wiemer

Gohlke

. Contribution of kinins to the cardiovascular actions of angiotensin-converting enzyme inhibitors. Pharmacol Rev 1995; 47: 25–49.

32.

Zafari

Ushio-Fukai

Akers

. Role of NADH/NADPH oxidase-derived H2O2 in angiotensin II-induced vascular hypertrophy. Hypertension 1998; 32: 488–495.

33.

Dijkhorst-Oei

Stroes

Koomans

. Acute simultaneous stimulation of nitric oxide and oxygen radicals by angiotensin II in humans in vivo. J Cardiovasc Pharmacol 1999; 33: 420–424.