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Diuretic and natriuretic actions of melanin concentrating hormone in conscious sheep
1Howard Florey Institute of Experimental Physiology and Medicine, University of Melbourne, Australia.
Abstract:
Melanin concentrating hormone (MCH) is a 19 amino-acid peptide expressed in high concentrations within the dorso-lateral hypothalamus of rats, sheep and man. MCH regulates skin colour and ACTH release in teleost fish, however, its physiological relevance in mammals is unclear. The present study examined the cardiovascular and metabolic actions of intracerebroventricular (i.c.v.) infusion of MCH, and the pro-MCH derived peptide Neuropeptide-E-I (NEI), in conscious, chronically instrumented sheep. Human MCH (1-19) or NEI (1-13) was infused i.c.v. for 24 h into 6 sheep, and measurements were made every 10 min of arterial pressure, heart rate, cardiac output, stroke volume and peripheral blood flow/conductance. Recordings of water intake (H2Oin), urine volume (Uv), urinary Na (UNaV) and K excretion (UKV) were made, as well as hematocrit, plasma Na, K, osmolality, protein, glucose, ACTH, vasopressin, renin, endothelin, ANF, cortisol and aldosterone concentrations. After 24 h of infusion at 10 microg/h, MCH produced a significant increase in Uv from 0.8 +/- 0.2 to 1.4 +/- 0.3 l/day, together with an increase in UNaV from 56 +/- 8 to 107 +/- 14 mmol/day, and in UKV from 202 +/- 18 to 369 +/- 38 mmol/day. H2Oin was unchanged. Similar renal changes were observed during i.c.v. infusion of NEI. There was no change in any cardiovascular parameter, although hematocrit showed a large decrease with infusion of both peptides after 24 h infusion. Plasma osmolality increased from 291 +/- 1 to 295 +/- 1 mOsm/kg during MCH infusion, whereas total protein and plasma Na and K were unchanged. MCH increased plasma glucose from 3.4 +/- 0.2 to 3.8 +/- 0.2 mmol/l. Plasma aldosterone exhibited a 30-40% decrease following MCH or NEI infusion, whereas all other plasma concentrations remained unchanged. This study has shown that i.c.v. infusion of MCH or NEI can produce diuretic, natriuretic and kaliuretic changes in conscious sheep, triggered by a possible increase in plasma volume as indicated by the changes in hematocrit. These results, together with anatomical data reporting the presence of MCH/NEI in fluid regulatory areas of the brain, indicate that MCH/NEI may be an important peptide involved in the central control of fluid homeostasis in mammals.
Insights
Melanin concentrating hormone (MCH) and Neuropeptide-E-I (NEI) infusion in sheep increased urine output and electrolyte excretion, suggesting a role in mammalian fluid balance. These peptides may be key in the central regulation of homeostasis.
Area of Science:
- Neuroendocrinology
- Physiology
Background:
- Melanin concentrating hormone (MCH) is a hypothalamic peptide with unclear physiological roles in mammals, despite known functions in fish.
- MCH and its precursor-derived peptide Neuropeptide-E-I (NEI) are found in brain regions involved in fluid regulation.
Purpose of the Study:
- To investigate the cardiovascular and metabolic effects of intracerebroventricular (i.c.v.) infusion of MCH and NEI in conscious sheep.
- To determine the impact of MCH and NEI on fluid and electrolyte balance, and hormonal status.
Main Methods:
- Conscious sheep were chronically instrumented for continuous monitoring of cardiovascular parameters (arterial pressure, heart rate, cardiac output, stroke volume, peripheral blood flow).
- Intracerebroventricular infusion of human MCH (1-19) or NEI (1-13) was administered for 24 hours.
- Measurements included water intake, urine volume and electrolytes, hematocrit, and plasma concentrations of various hormones and metabolites.
Main Results:
- MCH and NEI infusions significantly increased urine volume, sodium excretion (natriuresis), and potassium excretion (kaliuresis).
- Cardiovascular parameters remained unchanged, but hematocrit decreased, suggesting a potential increase in plasma volume.
- Plasma glucose and osmolality increased during MCH infusion, while plasma aldosterone decreased significantly with both peptides.
Conclusions:
- Intracerebroventricular administration of MCH and NEI induces diuretic, natriuretic, and kaliuretic responses in conscious sheep.
- These findings suggest MCH and NEI play a role in the central control of fluid homeostasis in mammals, potentially mediated by plasma volume expansion.
- MCH/NEI may be significant peptides involved in regulating mammalian fluid balance through central mechanisms.