Modulatory effects of endothelin-1 on central cardiovascular control in rats.
In urethane-anesthetized and immobilized rats, modulatory effects of endothelin-1 (ET-1) on central cardiovascular control were examined. An injection of 0.1 pmol of ET-1 into the cisterna magna caused immediate increases in arterial pressure (AP), renal sympathetic nerve activity (RSNA), and heart rate (HR) that lasted for 5-45 min. At doses of 1 and 10 pmol, intracisternal ET-1 elicited initial increases (phase I) followed by decreases in these variables below the pre-injection level (phase II). At the dose of 1 or 10 pmol, the arterial baroreceptor reflex was suppressed during the latter part of phase I and during phase II. The three variables subsequently returned to, or often exceeded, pre-injection levels in 30 to 60 min and reflex activity recovered (phase III). However, AP often remained below control throughout the 2-h observation period. Essentially identical responses to intracisternal ET-1 were observed in unanesthetized precollicular decerebrated or urethane-anesthetized rats. Application of a piece of filter paper soaked with 1 pmol of ET-1 to the ventral surface of the medulla (VSM) caused the pattern of changes similar to the following intracisternal injection. A microinjection of 4 pmol of ET-1 into the nucleus tractus solitarius (NTS) caused a moderate increase in RSNA with a minute fall in AP. Intrathecal administration of ET-1 resulted in moderate changes in AP and RSNA at the dose as high as 100 pmol. We conclude that intracisternally administered ET-1 modulates tonic and reflex control of AP and sympathetic vasomotor activity and that the VSM appears to be involved critically in this modulation.
Kuwaki
T
T
Department of Physiology, Faculty of Medicine, University of Tokyo, Japan.
Koshiya
N
N
Cao
W H
WH
Takahashi
H
H
Terui
N
N
Kumada
M
M
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002320:Cardiovascular Physiological Phenomena; D002319:Cardiovascular System / Q000187:drug effects*; D002490:Central Nervous System / Q000187:drug effects* / Q000502:physiology; D016232:Endothelins / Q000008:administration & dosage / Q000494:pharmacology*; D006339:Heart Rate / Q000187:drug effects; D007668:Kidney / Q000294:innervation; D008297:Male; D008845:Microinjections; D011311:Pressoreceptors / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D013564:Sympathetic Nervous System / Q000187:drug effects
D016232:Endothelins