TY - JOUR
T1 - Cardiovascular effects of neurotension and some analogues on rats
AU - Di Paola, Eugenio D.
AU - Richelson, Elliott
N1 - Funding Information:
This work was supported by Mayo Foundation and Grant MH 27692 from the U.S.P.H.S.
PY - 1990/1/17
Y1 - 1990/1/17
N2 - When administered in vivo into the femoral vein of normotensive rats, neurotensin, neurotensin-(8-13), and [D-Lys8]neurotensin-(8-13) decreased diastolic blood pressure in a dose-dependent manner, without change in heart rate. All three peptides evoked tachyphylaxis and a triphasic depressor-pressor-depressor, response at higher doses. The rank order of potency was neurotensin > [D-Lys8]neurotensin-(8-13). In organ chamber experiments, both neurotensin and neurotensin-(8-13) at a range of concentrations which induced dose-dependent decreases in blood pressure, did not significantly change tension in rat aorta rings with or without endothelium. In contrast, [D-Lys8]neurotensin-(8-13) induced weak dose-dependent relaxation of both rings with or without endothelium. However, this effect was not obtained at concentrations able to decrease the blood pressure. Indomethacin did not change the vasodilator effect of [D-Lys8]neurotensin-(8-13). There was no correlation between the vasodilator effect of this peptide and its ability to decrease blood pressure. These experiments suggest that the hypotension was not due to a direct vasodilator effect on the smooth muscle. In addition, since the rank order of peptide potency was opposite of those found in previous studies of second messenger synthesis and binding to neural tissue, these data suggest that there is a second receptor for neurotensin or that neurotensin can also bind to a different unknown receptor.
AB - When administered in vivo into the femoral vein of normotensive rats, neurotensin, neurotensin-(8-13), and [D-Lys8]neurotensin-(8-13) decreased diastolic blood pressure in a dose-dependent manner, without change in heart rate. All three peptides evoked tachyphylaxis and a triphasic depressor-pressor-depressor, response at higher doses. The rank order of potency was neurotensin > [D-Lys8]neurotensin-(8-13). In organ chamber experiments, both neurotensin and neurotensin-(8-13) at a range of concentrations which induced dose-dependent decreases in blood pressure, did not significantly change tension in rat aorta rings with or without endothelium. In contrast, [D-Lys8]neurotensin-(8-13) induced weak dose-dependent relaxation of both rings with or without endothelium. However, this effect was not obtained at concentrations able to decrease the blood pressure. Indomethacin did not change the vasodilator effect of [D-Lys8]neurotensin-(8-13). There was no correlation between the vasodilator effect of this peptide and its ability to decrease blood pressure. These experiments suggest that the hypotension was not due to a direct vasodilator effect on the smooth muscle. In addition, since the rank order of peptide potency was opposite of those found in previous studies of second messenger synthesis and binding to neural tissue, these data suggest that there is a second receptor for neurotensin or that neurotensin can also bind to a different unknown receptor.
KW - Aorta (rat)
KW - Blood pressure
KW - Heart rate
KW - Neurotensin
KW - Neurotensin analogues
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U2 - 10.1016/0014-2999(90)90565-N
DO - 10.1016/0014-2999(90)90565-N
M3 - Article
C2 - 2323349
AN - SCOPUS:0025164845
SN - 0014-2999
VL - 175
SP - 279
EP - 283
JO - European Journal of Pharmacology
JF - European Journal of Pharmacology
IS - 3
ER -