P. Vanbergen et al., A STUDY ON POSSIBLE MODULATING AND DIRECT EFFECTS OF GAMMA(2)-MSH ANDACTH-(1-24) ON THE CARDIOVASCULAR-SYSTEM OF THE RAT, Naunyn-Schmiedeberg's archives of pharmacology, 358(2), 1998, pp. 220-229
In conscious rats. yz-melanocyte-stimulating hormone (gamma(2)-MSH) do
se-dependently increases blood pressure and heart rate, whereas adreno
corticotropin-(1-24) [ACTH-(1-24)] dose-dependently decreases blood pr
essure, an effect which was accompanied by a reflectory tachycardia. A
s the exact mechanism involved in these cardiovascular effects of the
two melanocortins is as yet not known, we undertook a series of experi
ments to investigate the possibility that these peptides have modulati
ng or direct effect on the cardiovascular system of the rat. In pithed
rats gamma(2)-MSH, administered intravenously (i.v.) in doses of 5-20
0 nmol/kg, had no significant effect on systolic and diastolic blood p
ressure and on heart rate, whereas ACTH-(1-24), 5-500 nmol/kg, i.v., d
ose-dependently decreased blood pressure and increased heart rate. Inf
usion of gamma(2)-MSH, 10(-8) M, or ACTH-(1-24), 10(-6) M, In the isol
ated perfused rat heart did not significantly affect left ventricular
pressure or coronary flow. Pretreatment with either gamma(2)-MSH or AC
TH-(1-24) did not modify the responsiveness of the myocardium and coro
nary vasculature to salbutamol and phenylephrine. Neither gamma(2)-MSH
nor ACTH-(1-24) did affect the vascular contractile machinery of skin
ned vascular smooth muscles of the rabbit with respect to Ca2+ handlin
g in the cell, as measured by its sensitivity to exogenously applied C
a2+. gamma(2)-MSH had no effect on blood pressure and heart rate in pi
thed rats in which postganglionic sympathetic outflow was stimulated b
y 1,1-dimethyl-4-phenyl-piperazinium (DMPP, nor in pithed rats in whic
h preganglionic sympathetic outflow was stimulated electrically. A dos
e of 15 nmol/kg ACTH-(1-24)) had no significant influence on pregangli
onic outflow to the cardiac and vascular structures in pithed rats. Th
ese data show that gamma(2)-MSH does not exert its cardiovascular effe
cts via a peripheral site of action at the level of the vascular syste
m and the heart, nor directly on pre- or postganglionic sympathetic ou
tflow. These results are in support for the notion that the peptide ac
ts via a brain region localised outside the blood-brain barrier. The a
cute depressor effect of ACTH-(1-24), however, seems to be due to a di
rect effect on the vasculature in the periphery.