• K Sato, F Chatani, and T Ando.
• Drug Safety Research Laboratories, Takeda Chemical Industries, Limited, Osaka, Japan. Sato_Keiichiro@takeda.co.jp
• Chronobiol. Int. 1999 Mar 1; 16 (2): 171-83.

AbstractCircadian rhythmicity in the hypotensive effects of sodium nitroprusside (SNP) was determined to characterize the rhythmicity in hypotension mediated by nitric oxide (NO) donor in rats. When SNP was infused for 90 seconds every hour for 48 hours and the mean blood pressure was determined automatically by telemetry under light-dark conditions (LD), the degree of SNP-induced hypotension was shown to be minimal at the onset of the dark phase and to have marked circadian rhythmicity. The possible relationship between the circadian rhythm of the sympathetic nervous system (SNS) activity and SNP-induced hypotension was examined under LD conditions. The SNS activity assessed by blood pressure beat-to-beat variability analysis using the maximum entropy method (MEM) was higher at the preinfusion time at the onset of the dark phase than during the middle of the light phase. In addition, pretreatment with an alpha-blocker, phentolamine, followed by SNP infusion at the onset of the dark phase restored the SNP-induced hypotension and consequently dampened the daily variation in the degree of SNP-induced hypotension. The circadian rhythmicity determined by MEM was weakened, but persisted, in constant dark conditions (DD), suggesting partial involvement of endogenously driven circadian rhythms. In conclusion, the hypotensive effect of hourly infused SNP in rats was decreased in the dark phase in LD, especially at the onset of the dark phase, and clearly showed circadian rhythmicity in both LD and DD. The SNP-induced hypotension may be affected by rapid activation of the SNS at the onset of the dark phase in LD, and regulation of the circadian rhythm in SNP-induced hypotension in rats may be affected by both exogenous light stimuli and the endogenous biological clock.

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