Dr. Ron’s Research Review – March 30, 2011

This week’s research review focuses on erectile dysfunction and NSAIDs; and dietary nitrate.

Erectile dysfunction linked to aspirin and other NSAIDs

Daily use of aspirin and other nonsteroidal anti-inflammatory drugs, commonly known as NSAIDs, is associated with a 22 percent increase in the risk of erectile dysfunction, Kaiser researchers found in a study of more than 80,000 men in Southern California. (Gleason, Slezak et al. 2011)

Dietary nitrate attenuates oxidative stress, prevents cardiac and renal injuries, and reduces blood pressure in salt-induced hypertension

         (Carlstrom, Persson et al. 2010)

Dr. Ron


Articles

Regular nonsteroidal anti-inflammatory drug use and erectile dysfunction

            (Gleason, Slezak et al. 2011) Download

PURPOSE: Previous data suggest a potential relationship between inflammation and erectile dysfunction. If it is causal, nonsteroidal anti-inflammatory drug use should be inversely associated with erectile dysfunction. To this end we examined the association between nonsteroidal anti-inflammatory drug use and erectile dysfunction in a large, ethnically diverse cohort of men enrolled in the California Men's Health Study. MATERIALS AND METHODS: This prospective cohort study enrolled male members of the Kaiser Permanente managed care plans who were 45 to 69 years old beginning in 2002. Erectile dysfunction was assessed by questionnaire. Nonsteroidal anti-inflammatory drug exposure was determined by automated pharmacy data and self-reported use. RESULTS: Of the 80,966 men in this study 47.4% were considered nonsteroidal anti-inflammatory drug users based on the definitions used and 29.3% reported moderate or severe erectile dysfunction. Nonsteroidal anti-inflammatory drug use and erectile dysfunction strongly correlated with age with regular drug use increasing from 34.5% in men at ages 45 to 49 years to 54.7% in men 60 to 69 years old with erectile dysfunction increasing from 13% to 42%. The unadjusted OR for the association of nonsteroidal anti-inflammatory drugs and erectile dysfunction was 2.40 (95% CI 2.27, 2.53). With adjustment for age, race/ethnicity, smoking status, diabetes mellitus, hypertension, hyperlipidemia, peripheral vascular disease, coronary artery disease and body mass index, a positive association persisted (adjusted OR 1.38). The association persisted when using a stricter definition of nonsteroidal anti-inflammatory drug exposure. CONCLUSIONS: These data suggest that regular nonsteroidal anti-inflammatory drug use is associated with erectile dysfunction beyond what would be expected due to age and comorbidity.


Dietary nitrate attenuates oxidative stress, prevents cardiac and renal injuries, and reduces blood pressure in salt-induced hypertension

            (Carlstrom, Persson et al. 2010) Download

AIMS: Reduced bioavailability of endogenous nitric oxide (NO) is a central pathophysiological event in hypertension and other cardiovascular diseases. Recently, it was demonstrated that inorganic nitrate from dietary sources is converted in vivo to form nitrite, NO, and other bioactive nitrogen oxides. We tested the hypothesis that dietary inorganic nitrate supplementation may have therapeutic effects in a model of renal and cardiovascular disease. METHODS AND RESULTS: Sprague-Dawley rats subjected to unilateral nephrectomy and chronic high-salt diet from 3 weeks of age developed hypertension, cardiac hypertrophy and fibrosis, proteinuria, and histological as well as biochemical signs of renal damage and oxidative stress. Simultaneous nitrate treatment (0.1 or 1 mmol nitrate kg(1) day(1)), with the lower dose resembling the nitrate content of a diet rich in vegetables, attenuated hypertension dose-dependently with no signs of tolerance. Nitrate treatment almost completely prevented proteinuria and histological signs of renal injury, and the cardiac hypertrophy and fibrosis were attenuated. Mechanistically, dietary nitrate restored the tissue levels of bioactive nitrogen oxides and reduced the levels of oxidative stress markers in plasma (malondialdehyde) and urine (Class VI F2-isoprostanes and 8-hydroxy-2-deoxyguanosine). In addition, the increased circulating and urinary levels of dimethylarginines (ADMA and SDMA) in the hypertensive rats were normalized by nitrate supplementation. CONCLUSION: Dietary inorganic nitrate is strongly protective in this model of renal and cardiovascular disease. Future studies will reveal if nitrate contributes to the well-known cardioprotective effects of a diet rich in vegetables.


References

Carlstrom, M., A. E. Persson, et al. (2010). "Dietary nitrate attenuates oxidative stress, prevents cardiac and renal injuries, and reduces blood pressure in salt-induced hypertension." Cardiovasc Res 89(3): 574-85.

Gleason, J. M., J. M. Slezak, et al. (2011). "Regular nonsteroidal anti-inflammatory drug use and erectile dysfunction." J Urol 185(4): 1388-93.