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Effects of central endothelin-1 in normotensive and spontaneously hypertensive rats
T I Ponomareva1, O N Khokhlova, E A Tukhovskaya
1Laboratory of Biological Tests, M. M. Shemyakin and Yu. A. Ovchinnikov Institute of Bioorganic Chemistry (Pushchino Branch), Russian Academy of Sciences, Pushchino.
Abstract:
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.