Hypotensive peptides vascular effects

Another Beecham compound, BRL 13776 (25) has shown antihypertensive properties due to noradrenaline depletion in DOCA rats and renal hypertensive cats.98 Only the medulla/pons region of brain showed significant drops in noradrenaline, in contrast to reserpine. There were no behavioural effects and the compound is being taken to clinical trial. A novel hypotensive peptide, hypotensin, has been isolated from the venom of the Western diamondback rattlesnake.99 It contains approximately 20 amino-acid residues and appears unrelated to the kinins. The hypotensive effect is said to be dose-related after oral administration in normal rats and SHRs and is not consequent upon histamine release. Brief details of a clinical trial of a PGEp analogue (26) are available.100 Eleven of seventeen hypertensives responded with lower blood pressure to oral doses (10-20 pig) of 26. A recent studylOl of the marked antihypertensive properties of the diuretic Indapamide (27)(SE 1520, Servier) in rats and cats shows it to reduce vascular reactivity on chronic dosing. 

When CGRP is injected into the central nervous system, it produces a variety of effects, including hypertension and suppression of feeding. When injected into the systemic circulation, the peptide causes hypotension and tachycardia. The hypotensive action of CGRP results from the potent vasodilator action of the peptide indeed, CGRP is the most potent vasodilator yet discovered. It dilates multiple vascular beds, but the coronary circulation is particularly sensitive. 

NPY produces a variety of central nervous system effects, including increased feeding (it is one of the most potent orexigenic molecules in the brain), hypotension, hypothermia, respiratory depression, and activation of the hypothalamic-pituitary-adrenal axis. Other effects include vasoconstriction of cerebral blood vessels, positive chronotropic and inotropic actions on the heart, and hypertension. The peptide is a potent renal vasoconstrictor and suppresses renin secretion, but can cause diuresis and natriuresis. Prejunctional neuronal actions include inhibition of transmitter release from sympathetic and parasympathetic nerves. Vascular actions include direct vasoconstriction, potentiation of the action of vasoconstrictors, and inhibition of the action of vasodilators. 

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