Nocturnal Increase in Plasma cGMP Levels in Humans

Abstract

The circadian dynamics of responses to cyclic guanosine 3',5'-monophosphate (cGMP) in in vitro experiments and the stimulating effects of the pineal hormone melatonin on cGMP levels both in vitro and in vivo provoked an investigation into the diurnal pattern of occurrence of this second messenger in human plasma and its correlation with plasma melatonin levels. Plasma cGMP levels were measured in 9 normal human subjects who were over 50 years of age. Samples were obtained hourly through a 20-h period (11 a.m. to 7 a.m.) that included the subjects' habitual hours of nocturnal sleep; physical activity was kept to a minimum during the daylight hours. The area under the time-plasma cGMP concentration curve showed a significant increase during the period of nocturnal sleep compared to that observed during the period of daytime wakefulness. The individual temporal pattern of the nocturnal rise in plasma cGMP differed among the subjects; however, the initial increase typically was observed soon after bedtime. No significant correlation was observed between individual nocturnal plasma melatonin levels and cGMP levels.

The possible role of human milk nucleotides as sleep inducers

“…This nucleotide is a precursor of another intracellular messenger (cGMP) which, during the night, is involved in the secretion of the hormone melatonin, thereby inducing and entraining nocturnal rest. 13,38,39 Our chronobiological study showed this nucleotide to have a clear circadian rhythm, with the acrophase in the final hours of darkness, at 05:08 (an acrophase that is very similar to that reported by Skala et al 36 ) and a MESOR of 3.63 µg/ml.…”

“…12 Human studies have shown that cGMP plasma concentrations rise when the subject goes to bed and remain high throughout the night, reflecting its role in stimulating the secretion of the pineal hormone melatonin. 13,14 Recently there has been growing interest in studying nucleotides in the diet, since they seem to play an important role in human nutrition at different stages of life. This is especially so in infancy, as they influence neonatal development by the synthesis of phospholipids, by modifying the microflora and repairing any damage in the gut, and also by participating in the T-lymphocyte mediated immune response.…”

Increased Plasma cGMP in a Family With Autosomal Recessive Retinitis Pigmentosa Due to Homozygous Mutations in the PDE6A Gene

“…[56][57][58][59][60][61][62][63] Our control cGMP plasma levels at approximately 80 nM therefore compare relatively well with this.…”

“…Still, at this point we cannot claim that the higher level is a direct consequence of the disease. Differential blood cGMP levels have previously been seen in a variety of situations, for instance, in connection with natriuretic drugs for acute heart failure, 58 blood pressurealtering drugs, 59 preeclampsia, 60 migraine, 61 and in relation to the circadian rhythm, 63 where the cGMP levels may in turn be dependent on melatonin levels. 62 With a possible connection to this, the ROC specificity aspect indicates that some healthy subjects may appear as having the disease.…”

cGMP-Dependent Protein Kinase Type I Is Implicated in the Regulation of the Timing and Quality of Sleep and Wakefulness

“…Variations of brain NO levels during the sleep-wake cycle were observed in rats [7], [8], and plasma levels of cGMP, a second messenger downstream of NO (reviewed in [9]), were found to be elevated at night in humans [10]. Moreover, NO and cGMP have been suggested to be involved in the modulation of circadian rhythmicity [11].…”