Cardiovascular and neurohormonal effects of intravenous adrenomedullin in conscious rabbits.
Adrenomedullin is a vasodilative peptide and shows slight homology with calcitonin gene-related peptide. In the present study, we investigated the effects of adrenomedullin on cardiovascular and neurohormonal responses in 13 conscious rabbits. The animals were chronically instrumented with bipolar electrodes on the left renal sympathetic nerve. Intravenous administration of human adrenomedullin (10, 100, 1,000, and 3,000 pmol/kg, n = 6) caused a dose-dependent reduction in mean arterial pressure (0 +/- 2, -1 +/- 2, -19 +/- 2, and -29 +/- 4 mmHg, respectively) concomitant with increases in heart rate, renal sympathetic nerve activity, plasma renin activity, and plasma norepinephrine. The significant reduction in mean arterial pressure induced by 1,000 pmol/kg of adrenomedullin occurred within 1 min after injection and lasted for 15 min (n = 7). In contrast, the significant increases in heart rate and renal sympathetic nerve activity lasted for more than 50 min. When mean arterial pressure was decreased by 15 mmHg by adrenomedullin, the increases in heart rate and renal sympathetic nerve activity were 53 +/- 8 beats/min and 78 +/- 13%, respectively, which were significantly smaller than those induced by intravenous injection of sodium nitroprusside (102 +/- 14 beats/min and 155 +/- 34%, respectively). These results suggest that intravenous adrenomedullin exerts a hypotensive action that is associated with the attenuated reflex-mediated sympathetic activation.
Fukuhara
M
M
Second Department of Internal Medicine, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
Tsuchihashi
T
T
Abe
I
I
Fujishima
M
M
D053607:Adrenomedullin; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D002319:Cardiovascular System / Q000187:drug effects*; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D007275:Injections, Intravenous; D007668:Kidney / Q000294:innervation; D008297:Male; D018377:Neurotransmitter Agents / Q000097:blood*; D010455:Peptides / Q000494:pharmacology*; D011817:Rabbits; D013564:Sympathetic Nervous System / Q000187:drug effects
D000959:Antihypertensive Agents; D018377:Neurotransmitter Agents; D010455:Peptides; D053607:Adrenomedullin