Sildenafil acts on the central nervous system increasing sympathetic activity

• Published in: Journal of applied physiology (1985) 2008-06, Vol.104 (6), p.1683-1689
• Main Authors: Fazan, Rubens, Jr, Huber, Domitila A, Silva, Carlos Alberto A, Dias da Silva, Valdo J, Salgado, Maria Cristina O, Salgado, Helio C
• Format: Article
• Language: English
• Subjects: Animals; Baroreflex - drug effects; Biological and medical sciences; Blood Pressure - drug effects; Cardiovascular System - drug effects; Cardiovascular System - innervation; Central Nervous System - drug effects; Effects; Fundamental and applied biological sciences. Psychology; Heart rate; Heart Rate - drug effects; Injections, Intraventricular; Male; Nervous system; Phosphodiesterase Inhibitors - administration & dosage; Phosphodiesterase Inhibitors - pharmacology; Piperazines - administration & dosage; Piperazines - pharmacology; Purines - administration & dosage; Purines - pharmacology; Rats; Rats, Wistar; Rodents; Sexual disorders; Sildenafil Citrate; Spectrum analysis; Sulfones - administration & dosage; Sulfones - pharmacology; Sympathetic Nervous System - drug effects; Time Factors; Vasodilator Agents - administration & dosage; Vasodilator Agents - pharmacology; Veins & arteries
• ISSN: 8750-7587; 1522-1601
• DOI: 10.1152/japplphysiol.01142.2007

Departments of 1 Physiology and 2 Pharmacology, School of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, São Paulo, and 3 Department of Biological Sciences, Federal University of the Triângulo Mineiro, Uberaba, Minas Gerais, Brazil Submitted 25 October 2007 ; accepted in final form 31 March 2008 Sildenafil induces vasodilation and is used for treating erectile dysfunction. Although its influence on resting heart function appears to be minimal, recent studies suggest that sildenafil can increase sympathetic activity. We therefore tested whether sildenafil injected into the central nervous system alters the autonomic control of the cardiovascular system in conscious rats. The effect of sildenafil citrate injected into the lateral cerebral ventricle was evaluated in conscious rats by means of the recording of lumbar sympathetic nerve activity (LSNA), spectral analysis of systolic arterial pressure and heart rate variability, spontaneous baroreflex sensitivity, and baroreflex control of LSNA. Intracerebroventricular (ICV, 100 µg/5 µl) administration of sildenafil caused remarkable tachycardia without significant change in basal arterial pressure and was associated with a conspicuous increase (47 ± 14%) in LSNA. Spectral analysis demonstrated that systolic arterial pressure oscillations in the low frequency (LF) range were increased (from 6.3 ± 1.5 to 12.8 ± 3.8 mmHg 2 ), whereas the high frequency (HF) range was not affected by ICV administration of sildenafil. Sildenafil increased pulse interval oscillations at LF and decreased them at HF. The LF-HF ratio increased from 0.04 ± 0.01 to 0.17 ± 0.06. Spontaneous baroreflex sensitivity measured by the sequence method and the baroreflex relationship between mean arterial pressure and LSNA were not affected by ICV administration of sildenafil. In conclusion, sildenafil elicited an increase in sympathetic nerve activity that is not baroreflex mediated, suggesting that this drug is able to elicit an autonomic imbalance of central origin. This finding may have implications for understanding the cardiovascular outcomes associated with the clinical use of this drug. arterial pressure; heart rate; sympathetic drive; spectral analysis Address for reprint requests and other correspondence: H. C. Salgado, Dept. of Physiology, School of Medicine of Ribeirão Preto-USP, Av. Bandeirantes 3900, 14049-900, Ribeirão Preto, SP Brazil (e-mail: hcsalgad{at}fmrp.usp.br )