Lack of circadian rhythm of plasma concentrations of vasoactive intestinal peptide in patients with orthotopic heart transplants.

Abstract

Objective-To study the circadian pattern of plasma concentrations of vasoactive intestinal peptide (VIP) in patients with orthotopic heart transplants. Circulating VIP is known to have neural and immunological sources. Patients and methods-13 patients with orthotopic heart transplants were studied 12-53 months (mean 318 months) after operation. All were haemodynamically compensated and had no histological evidence of rejection. They were being treated with cyclosporin, azathioprine, and prednisone. Ten healthy individuals were studied as controls. Circulating VIP was assayed six times within a 24h period. Time qualified data were analysed by ANOVA and the cosinor method. Student's t test for unpaired data and Bingham's test for cosinorderived parameters were used for statistical comparisons. Results-Plasma concentrations of VIP were lower in the patients with orthotopic heart transplants than in the controls (p < 0.001). ANOVA and the cosinor method respectively showed a statistically significant within-day variability and circadian rhythm in the controls but not in the patients with heart transplants.Discussion-The low plasma concentrations of VIP in the patients with heart transplants could be the result of the lack of contribution by the cardiac VlPergic fibres, a reduction of VIP release by the pharmacologically suppressed immune system, the inhibitory effects of cyclosporin on neural fimction and humoral secretions, and the effects of negative feedback on VIP release of high concentrations of atrial natriuretic peptide. The lack of the circadian rhythm suggests a structural disorder, which should be firther investigated. (Br HeartrJ 1993;70:363-365) Vasoactive intestinal peptide (VIP) is widely distributed throughout the central and peripheral nervous system where it acts as a neurotransmitter or neuromodulator or both.1-11 The cardiovascular system of various mammalian species is innervated by VIP fibres, which are more dense in the sinoatrial node, atrioventricular node, atrial myocardium, and epicardial coronary arteries and less dense in the ventricular myo-cardium.12-"5 The physiological role of endo-genous VIP in the cardiovascular system has not been clearly established. In adult animals and humans intravenous VIP causes vasodilatation of the systemic and coronary arteries and has positive inotropic and chronotropic effects.l6-22VIP is assumed to be a neurotransmitter rather than a bloodborne hormone and its circulating concentrations probably represent an overflow of the neuronal release. Plasma concentrations of VIP were increased in severe hepatic failure23 and cardiac failure2425 but unchanged in patients with circulatory shock24 or myocardial infarction.24Patients with heart transplants show abnormal circulating concentrations or circadian rhythmicity or both of the hormones responsible for the regulation of the cardiovascular system.26In the present study we investigated the hypothesis that, like other vasoactive peptides, VIP release is also impaired. We used a chronobiological prot...

Effect of Sodium Depletion by Frusemide on Tissue Concentrations and Metabolism of VIPa

“…VIP is synthesized and secreted by the heart. 7 However, experiments in which injection of radioiodinated VIP ( 125 I‐VIP) and 125 I were compared showed the same pattern of accumulation of radioactivity for both. 8 This suggests that the heart is not a significant site of VIP metabolism.…”

“…The heart was chosen as it secretes VIP, being responsible for diurnal variations in plasma concentration of VIP. 7 Concentrations of VIP in the lung and kidney were also measured as these are the major sites for removal of VIP from the circulation. 8…”

Proteomics - Human Diseases and Protein Functions

“…Rhythms illustrated here are based on the references listed in Table 2. (Cugini et al, 1992) § (Cugini et al, 1993) Table 2. Circadian rhythms in neuro/hormones in humans…”

“…It has a circadian rhythm with a peak before sleep time (20:00) and a trough later at night (0:00) (Cugini et al, 1991). The rhythm of this peptide is lost in patients with orthotopic heart transplant (Cugini et al, 1993).…”