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J Appl Physiol (April 3, 2008). doi:10.1152/japplphysiol.01142.2007
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Submitted on October 25, 2007
Accepted on March 31, 2008

SILDENAFIL ACTS ON THE CENTRAL NERVOUS SYSTEM INCREASING SYMPATHETIC ACTIVITY

Rubens Fazan Jr1, Domitila A. Huber1, Carlos A Silva1, Valdo Jose Dias da Silva2, Maria Cristina Oliveira Salgado3, and Helio Cesar Salgado1*

1 Physiology, School of Medicine of Ribeirao Preto, Brazil
2 Biological Sciences, School of Medicine of the Triangulo Mineiro, Uberaba, Minas Gerais, Brazil
3 Pharmacology, University of Sao Paulo, Ribeirao Preto, Sao Paulo, Brazil

* To whom correspondence should be addressed. E-mail: hcsalgad{at}fmrp.usp.br.

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 CNS 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 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 mmHg2), while 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.







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