K. Nakamura et al., Central effects of endothelin and its antagonists on sympathetic and cardiovascular regulation in SHR-SP, J CARDIO PH, 33(6), 1999, pp. 876-882
Citations number
36
Categorie Soggetti
Cardiovascular & Respiratory Systems","Cardiovascular & Hematology Research
Intracerebroventricular injections of endothelin-1 (ET-1) are reported to c
ause dose-related increases in sympathetic nerve activity and blood pressur
e in anesthetized normotensive rats. These studies were performed to determ
ine the following: which endothelin receptor, A or B, is involved in mediat
ing sympathetic and cardiovascular effects of ET-1 injected centrally; whet
her central endothelin tonically participates in blood pressure regulation
in normotensive rats; and whether the altered endothelin system in the cent
ral nervous system contributes to blood pressure elevation in hypertensive
rats. ET-1, ET-A antagonist (BQ-123), or ET-B antagonist (RES-701-1) was in
jected into the lateral cerebral ventricle (i.c.v.) of urethane-anesthetize
d normotensive Wistar and Wistar-Kyoto (WKY) rats, spontaneously hypertensi
ve rats (SHRs), and stroke-prone SHRs (SHR-SPs). In Wistar rats, i.c.v. inj
ections of ET-1 (1, 5, 10 pmol) consistently increased sympathetic nerve ac
tivity, thereby elevating blood pressure in a dose-related manner. The pres
ser responses induced by i.c.v. ET-1 were abolished after intravenous pretr
eatment with phentolamine. Neither ET-A nor ET-B antagonist, when injected
centrally, altered basal levels of sympathetic nerve activity, heart rate,
or blood pressure in Wistar rats. However, sympathetic activation and press
er responses induced by i.c.v. injection of endothelin were completely abol
ished after i.c.v. pretreatment with ET-A antagonist but were unaffected af
ter pretreatment with ET-B antagonist. Although i.c.v. injections of ET-1 i
ncreased sympathetic nerve activity and blood pressure in WKY rats, SHRs, a
nd SHR-SPs, the magnitudes of these responses did not differ among these th
ree groups. In contrast, i.c.v, injections of ET-A antagonist decreased sym
pathetic nerve activity, blood pressure, and heart rate only in SHR-SPs, bu
t not in WKY rats and SHRs. In addition, the depressor effects of i.c.v. ET
-A antagonist in SHR-SPs were ascertained while these rats were awake. In s
ummary, i.c.v. injections of ET-1 increased sympathetic nerve activity and
blood pressure via ET-A receptors but not via ET-B receptors. Central ET mi
ght tonically activate sympathetic nerve activity to thereby contribute to
blood pressure elevation in SHR-SPs, but not in WKY rats and SHRs.