Digital Plethysmography and Arginine Metabolism in Prehypertension—Effect of Nebivolol Therapy

Abstract

Prehypertension is an important phenotype for cardiovascular risk and development of established hypertension. To better understand the early circulatory changes in this group, the authors studied 34 patients with prehypertension (blood pressure 120-139/80-89 mm Hg) using digital plethysmography for measurement of blood flow and reactive hyperemic index (RHI). Arterial augmentation index (AI) was also measured. Because prehypertension is associated with endothelial dysfunction and decreased availability of nitric oxide (NO), indices of arginine metabolism (L-arginine, asymmetric dimethylarginine (ADMA), symmetric dimethylarginine, and L-citrulline) were measured. Nebivolol (5 mg/ d), a vasodilating b 1 -antagonist with b 3 -agonist activity, was studied in a double-blind fashion for 8 weeks. Nebivolol increases the bioavailability of NO. Prehypertension was associated with normal RHI and baseline digital blood flow. AI was abnormal and associated with diastolic blood pressure. ADMA concentration was increased at baseline. After 8 weeks of nebivolol therapy, RHI, ADMA, symmetric dimethylarginine, and AI showed no significant change, but digital blood flow and L-citrulline levels were significantly increased. Prehypertension is associated with increased ADMA and evidence of increased arterial stiffness and preserved RHI. Nebivolol therapy is associated with digital vasodilation and increased NO production, as depicted by increased levels of L-citruline and mean digital blood flow.

Are All β‐Blockers the Same? Nebivolol Vasodilator Properties and Evidence for Relevance in Treatment of Hypertension

“…In addition, different classes of antihypertensive drugs have different effects on the central BP and arterial stiffness . However, the current study did not show any beneficial effect of nebivolol treatment on AI despite reductions in BP . Vaz‐de‐Melo and colleagues demonstrated that nebivolol reduced central BP but not AI.…”

“…In this issue of The Journal of Clinical Hypertension , Kandavar and colleagues studied the circulatory changes in prehypertensive patients by digital plethysmography for measurement of blood flow and reactive hyperemic index (RHI). Additionally, they measured augmentation index (AI) and the effect of nebivolol therapy on L‐arginine, asymmetric dimethlyarginine (ADMA), symmetric dimethlyarginine (SDMA), and L‐citrulline levels after 8 weeks in a blinded fashion.…”

“…They concluded that prehypertension is associated with increased ADMA and evidence of increased arterial stiffness and preserved RHI. Nebivolol therapy is associated with digital vasodilatation and increased nitric oxide production, as depicted by increased levels of L‐citrulline and mean digital blood flow …”

Pleiotropic Effect of Nebivolol: Recent Data

“…Это было пока-зано методами измерения реактивного гиперемиче-ского индекса и среднего давления в артериях паль-цев. Такой эффект объясняло повышение циркулирующих в крови уровней 1-цитрулина и асимметричного диметиларгинина [6]. Davis et al (2013) также исследовали лиц с предгипертензией.…”

Nebivolol Effects on Nitric Oxide Levels, Blood Pressure, and Renal Function in Kidney Transplant Patients

“…12,13 Unfortunately, calcineurin inhibitors (CNIs), the cornerstone of current antirejection immunosuppression, can negate these beneficial effects through various mechanisms including elaboration of vasoconstrictor cytokines and reduction in vasodilator prostaglandins and NO. 3,5,[17][18][19][20] CNIs are also implicated in the pathogenesis of posttransplant hypertension through activation of the sympathetic nervous and renin-angiotensin-aldosterone systems, intense afferent arteriolar vasoconstriction, and sodium retention. [21][22][23] In the absence of a robust, evidence-based guideline on the management of post-transplant hypertension, 11,24 clinicians have a wide latitude in selecting drugs for treating hypertension in transplant recipients.…”