Effects of central endothelin-1 in normotensive and spontaneously hypertensive rats.
Changes in blood pressure and sympathetic nerve activity induced by local injection of endothelin-1 into the rostroventrolateral medulla were studied in narcotized stroke-prone spontaneously hypertensive rats (SHRSP) and normotensive WKY rats. Endothelin-1 produced similar biphasic response in both rat strains: a transient increase in blood pressure and sympathetic nerve activity followed by progressive hypotension and bradycardia. Pretreatment with ETB-receptor antagonist BQ788 inhibited sympathetic activation induced by endothelin-1, while pretreatment with the ETA-receptor antagonist N-acetyl-[D-Trp16]-endothelin-1 abolished the subsequent hypotension. The antihypotensive effect of ETA-receptor blockade was most effective in normotensive rats. Our findings suggest that cardiovascular disorders in SHRSP rats can be related to peculiarities in the rostroventrolateral medullar endothelin system.
Ponomareva
T I
TI
Laboratory of Biological Tests, M. M. Shemyakin and Yu. A. Ovchinnikov Institute of Bioorganic Chemistry (Pushchino Branch), Russian Academy of Sciences, Pushchino.
Khokhlova
O N
ON
Tukhovskaya
E A
EA
Murashov
A M
AM
D000818:Animals; D000959:Antihypertensive Agents / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects*; D019332:Endothelin-1 / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology*; D006339:Heart Rate / Q000187:drug effects*; D008297:Male; D008526:Medulla Oblongata / Q000187:drug effects; D009842:Oligopeptides / Q000378:metabolism; D010880:Piperidines / Q000378:metabolism; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D017466:Receptors, Endothelin / Q000378:metabolism; D013564:Sympathetic Nervous System / Q000187:drug effects* / Q000378:metabolism
D000959:Antihypertensive Agents; D019332:Endothelin-1; D009842:Oligopeptides; D010880:Piperidines; D017466:Receptors, Endothelin; C086539:BQ 788