Article date: September 2002
By: Stephanie W Watts, Gregory D Fink, Carrie A Northcott, James J Galligan in Volume 137, Issue 1, pages 69-79
Deoxycorticosterone acetate (DOCA) salt hypertension is associated with an endothelin‐1 (ET‐1)‐dependent increase in arterial resistance and mean circulatory filling pressure. Contraction of endothelium‐intact arteries and veins from sham and DOCA‐salt hypertensive rats to agonists of the ETA (ET‐1(1–31)) and ETB receptor (sarafotoxin 6c; S6c) was investigated in tissue baths as was expression of mRNA for ET‐1 and mRNA and protein for the ETA and ETB receptor.
ET‐1(1–31) contracted aorta and vena cava from sham rats with a 30 fold lower potency than ET‐1. Contraction was not altered by the ETB receptor antagonist BQ788 (100 nM) but was abolished by the ETA receptor antagonist ABT‐627 (30 nM).
In DOCA‐salt thoracic aorta, maximum contraction to ET‐1 and ET‐1(1–31) was reduced (36.6±6.3 and 13.3±4.4% of sham response, respectively); aorta did not contract to S6c.
In vena cava from DOCA‐salt rats, contraction to ET‐1 and ET‐1(1–31) was not reduced compared to sham contraction; vena cava from sham and DOCA‐salt rats contracted to S6c with a similar potency.
Real time RT–PCR revealed that prepro ET‐1 mRNA was increased 6.6±3.3 fold and 8.7±3.9 fold greater in DOCA‐salt aorta and vena cava, respectively, compared to sham. Vena cava expressed a higher content of ETA and ETB receptor mRNA than aorta (P<0.05), but no differences were observed between sham and DOCA‐salt tissues. ETA and ETB receptor protein was identified in all tissues. Immunoreactive ETA receptor, observed as a 65, 30 and 28 kDa bands, was expressed 400% greater in DOCA‐salt aorta compared to sham, but was not altered in vena cava. Immunoreactive ETB receptor, observed as 120, 45 and 30 kDa bands, tended to be higher in vena cava compared to aorta, but was not different in sham and DOCA‐salt vena cava.
These results suggest that ETA receptor function is impaired in aorta but not vena cava of DOCA‐salt rats. The ETB receptor was present in the aorta but, unlike in veins, does not mediate contraction directly. A sustained response to ET‐1 in the venous circulation may contribute to the elevated blood pressure in the DOCA‐salt model.
Deoxycorticosterone acetate (DOCA) salt hypertension is associated with an endothelin‐1 (ET‐1)‐dependent increase in arterial resistance and mean circulatory filling pressure. Contraction of endothelium‐intact arteries and veins from sham and DOCA‐salt hypertensive rats to agonists of the ETA (ET‐1(1–31)) and ETB receptor (sarafotoxin 6c; S6c) was investigated in tissue baths as was expression of mRNA for ET‐1 and mRNA and protein for the ETA and ETB receptor.
ET‐1(1–31) contracted aorta and vena cava from sham rats with a 30 fold lower potency than ET‐1. Contraction was not altered by the ETB receptor antagonist BQ788 (100 nM) but was abolished by the ETA receptor antagonist ABT‐627 (30 nM).
In DOCA‐salt thoracic aorta, maximum contraction to ET‐1 and ET‐1(1–31) was reduced (36.6±6.3 and 13.3±4.4% of sham response, respectively); aorta did not contract to S6c.
In vena cava from DOCA‐salt rats, contraction to ET‐1 and ET‐1(1–31) was not reduced compared to sham contraction; vena cava from sham and DOCA‐salt rats contracted to S6c with a similar potency.
Real time RT–PCR revealed that prepro ET‐1 mRNA was increased 6.6±3.3 fold and 8.7±3.9 fold greater in DOCA‐salt aorta and vena cava, respectively, compared to sham. Vena cava expressed a higher content of ETA and ETB receptor mRNA than aorta (P<0.05), but no differences were observed between sham and DOCA‐salt tissues. ETA and ETB receptor protein was identified in all tissues. Immunoreactive ETA receptor, observed as a 65, 30 and 28 kDa bands, was expressed 400% greater in DOCA‐salt aorta compared to sham, but was not altered in vena cava. Immunoreactive ETB receptor, observed as 120, 45 and 30 kDa bands, tended to be higher in vena cava compared to aorta, but was not different in sham and DOCA‐salt vena cava.
These results suggest that ETA receptor function is impaired in aorta but not vena cava of DOCA‐salt rats. The ETB receptor was present in the aorta but, unlike in veins, does not mediate contraction directly. A sustained response to ET‐1 in the venous circulation may contribute to the elevated blood pressure in the DOCA‐salt model.
British Journal of Pharmacology (2002) 137, 69–79. doi:10.1038/sj.bjp.0704831
DOI: 10.1038/sj.bjp.0704831
View this article