TY - JOUR
T1 - Differential haemodynamic effects of endothelin receptor antagonist, SB 209670, in conscious hypertensive and normotensive rats
AU - Bunting, Michael W.
AU - Widdop, Robert E.
PY - 1999/9/17
Y1 - 1999/9/17
N2 - Endothelin has been implicated in the pathogenesis and/or maintenance of hypertension. Endothelin receptor antagonists lower blood pressure in the spontaneously hypertensive rat (SHR), but the regional haemodynamic effects of such drugs in the SHR remain unknown. The aim of this study was to examine the regional haemodynamic effects of the endothelin receptor antagonist, (±)-(1S,2R,3S)-3-(2-carboxymethoxy-4-methoxyphenyl)-1-(3,4- methylenedioxyphenyl)-5-(prop-1-yloxy)-indane-2-carboxylic acid (SB 209670), in SHR and Wistar-Kyoto (WKY) rats. Rats underwent a two-stage operation for implantation of Doppler flow probes and intravascular catheters. Recordings were made of mean arterial pressure (MAP), heart rate (HR) and renal (Ren), mesenteric (Mes) and hindquarters (HQ) blood flows and conductances (Cond). SHR and WKY received 4.5 h infusions of saline or SB 209670 (5 mg/kg priming dose+1 or 5 mg/kg/h, i.v.). SB 209670 lowered blood pressure in both SHR (- 23±2 mm Hg) and WKY rats (-13±1 mm Hg). In addition, a lower dose infusion of SB 209670 also had an antihypertensive effect in SHR (-15±5 mm Hg). In SHRs which received the higher dose of antagonist, Ren, Mes and HQ Cond were significantly increased as was the HQ Cond in a low-dose group. In WKY rats, SB 209670 decreased Ren blood flow whilst increasing Mes and HQ blood flows and Cond. SB 209670 also attenuated the regional vasoconstrictor effects of endothelin-1, except in the Mes circulation in SHR. This study illustrates that SB 209670 causes differential haemodynamic effects in SHR and WKY rats. In SHR, the antihypertensive effect of SB 209670 was accompanied by a generalised vasodilatation in the Ren, Mes and HQ vascular beds. In WKY rats, the hypotensive effect of SB 209670 was accompanied by Mes and HQ vasodilatation, but with Ren vasoconstriction. Thus, endothelin is involved in the maintenance of blood pressure and vascular tone in both SHR and WKY rats, but the haemodynamic profiles of these effects differ between the two strains.
AB - Endothelin has been implicated in the pathogenesis and/or maintenance of hypertension. Endothelin receptor antagonists lower blood pressure in the spontaneously hypertensive rat (SHR), but the regional haemodynamic effects of such drugs in the SHR remain unknown. The aim of this study was to examine the regional haemodynamic effects of the endothelin receptor antagonist, (±)-(1S,2R,3S)-3-(2-carboxymethoxy-4-methoxyphenyl)-1-(3,4- methylenedioxyphenyl)-5-(prop-1-yloxy)-indane-2-carboxylic acid (SB 209670), in SHR and Wistar-Kyoto (WKY) rats. Rats underwent a two-stage operation for implantation of Doppler flow probes and intravascular catheters. Recordings were made of mean arterial pressure (MAP), heart rate (HR) and renal (Ren), mesenteric (Mes) and hindquarters (HQ) blood flows and conductances (Cond). SHR and WKY received 4.5 h infusions of saline or SB 209670 (5 mg/kg priming dose+1 or 5 mg/kg/h, i.v.). SB 209670 lowered blood pressure in both SHR (- 23±2 mm Hg) and WKY rats (-13±1 mm Hg). In addition, a lower dose infusion of SB 209670 also had an antihypertensive effect in SHR (-15±5 mm Hg). In SHRs which received the higher dose of antagonist, Ren, Mes and HQ Cond were significantly increased as was the HQ Cond in a low-dose group. In WKY rats, SB 209670 decreased Ren blood flow whilst increasing Mes and HQ blood flows and Cond. SB 209670 also attenuated the regional vasoconstrictor effects of endothelin-1, except in the Mes circulation in SHR. This study illustrates that SB 209670 causes differential haemodynamic effects in SHR and WKY rats. In SHR, the antihypertensive effect of SB 209670 was accompanied by a generalised vasodilatation in the Ren, Mes and HQ vascular beds. In WKY rats, the hypotensive effect of SB 209670 was accompanied by Mes and HQ vasodilatation, but with Ren vasoconstriction. Thus, endothelin is involved in the maintenance of blood pressure and vascular tone in both SHR and WKY rats, but the haemodynamic profiles of these effects differ between the two strains.
KW - Blood flow, regional
KW - Dilatation
KW - Endothelin
KW - Hypertension
KW - SB 209670
KW - Vasoconstriction
UR - http://www.scopus.com/inward/record.url?scp=0032878073&partnerID=8YFLogxK
U2 - 10.1016/S0014-2999(99)00536-1
DO - 10.1016/S0014-2999(99)00536-1
M3 - Article
C2 - 10528129
AN - SCOPUS:0032878073
VL - 381
SP - 13
EP - 21
JO - European Journal of Pharmacology
JF - European Journal of Pharmacology
SN - 0014-2999
IS - 1
ER -