title: Cyclic guanosine monophosphate phosphodiesterase-5 inhibitor promotes an endothelium NO-dependent-like vasodilation in patients with refractory hypertension.
abstract: The nitric oxide/cyclic-guanosine 3',5'-monophosphate signaling cascade plays an essential role in cardiovascular homeostasis but its involvement in the pathophysiology of refractory hypertension is unclear. The acute vasodilatory effect of a single oral dose of a phosphodiesterase-5 inhibitor (sildenafil citrate) on the brachial artery dilatation was evaluated in 25 normal healthy volunteers (NL) and in 25 refractory hypertensive patients (RH). Endothelial and vascular smooth muscle functions were assessed two times. First, the brachial artery response to endothelium-dependent (flow-mediated dilatation [FMD]) and independent (glyceryl trinitrate [GTN]) stimuli was examined. The FMD in NL was 14.2+/-3.2% compared to 10.3+/-3.5% in RH (P<0.001) and the GTN-induced responses were 23.5+/-6.3 in NL compared to 18.4+/-5.7% in RH (P<0.001). Two weeks later, the brachial artery responses to FMD were determined before and after the administration of sildenafil citrate. Sildenafil caused a significant, slow and progressive dilatation of the brachial artery until 45 min after administration (4.7+/-3.0%, 6.7+/-3.0% and 9.4+/-3.9% after 15', 30' and 45', respectively, in RH and 3.7+/-1.9%, 7.4+/-2.7% and 10.1+/-3.0%, respectively, in NL). A second FMD stimulus, applied 45 min after ingesting 50mg of sildenafil resulted in an additional significant increase in the vasodilatory response (from 9.4+/-3.9% to 13.0+/-4.0% in RH; P<0.001 and from 10.1+/-3.0 to 14.6+/-4.1 in NL; P<0.001), but this was still significantly less than the response to GTN. Sildenafil citrate caused brachial artery vasodilatation similar to that caused by NO released during FMD in patients with refractory hypertension.
authors.affiliation: Laboratory of Cardiovascular Pharmacology, Department of Pharmacology, Faculty of Medical Sciences, State University of Campinas (UNICAMP), PO Box 6111, 13083-970 Campinas, SP, Brazil. yugarjuan@uol.com.br
authors.forename: Juan Carlos
authors.initials: JC
authors.lastname: Yugar-Toledo
authors.forename: Sílvia E
authors.initials: SE
authors.lastname: Ferreira-Melo
authors.forename: Fernanda M
authors.initials: FM
authors.lastname: Consolim-Colombo
authors.forename: Maria C
authors.initials: MC
authors.lastname: Irigoyen
authors.forename: Otávio Rizzi
authors.initials: OR
authors.lastname: Coelho
authors.forename: Heitor
authors.initials: H
authors.lastname: Moreno
mesh_terms: D015106:3',5'-Cyclic-GMP Phosphodiesterases / Q000378:metabolism; D000328:Adult; D006152:Cyclic GMP / Q000378:metabolism*; D054706:Cyclic Nucleotide Phosphodiesterases, Type 5; D004727:Endothelium / Q000378:metabolism*; D006801:Humans; D006973:Hypertension / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000378:metabolism*; D005996:Nitroglycerin / Q000627:therapeutic use; D010726:Phosphodiesterase Inhibitors / Q000378:metabolism / Q000627:therapeutic use; D010879:Piperazines / Q000378:metabolism / Q000627:therapeutic use; D011687:Purines / Q000378:metabolism / Q000627:therapeutic use; D015398:Signal Transduction / Q000502:physiology; D000068677:Sildenafil Citrate; D013450:Sulfones / Q000378:metabolism / Q000627:therapeutic use; D014664:Vasodilation / Q000502:physiology*; D014665:Vasodilator Agents / Q000378:metabolism / Q000627:therapeutic use
chemical_list: D010726:Phosphodiesterase Inhibitors; D010879:Piperazines; D011687:Purines; D013450:Sulfones; D014665:Vasodilator Agents; D009569:Nitric Oxide; D000068677:Sildenafil Citrate; D015106:3',5'-Cyclic-GMP Phosphodiesterases; D054706:Cyclic Nucleotide Phosphodiesterases, Type 5; C517381:PDE5A protein, human; D005996:Nitroglycerin; D006152:Cyclic GMP