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Blood pressure and vascular effects of endothelin blockade in chronic nitric oxide-deficient hypertension.
Hypertension. 1997 Mar; 29(3):763-9.H

Abstract

Because nitric oxide inhibits the synthesis and vasoconstrictor effect of endothelin-1, the effect of endothelin-1 may be enhanced under conditions of chronic inhibition of nitric oxide synthesis. We studied the effect of chronic therapy with bosentan, a combined endothelin-A/endothelin-B receptor antagonist, on blood pressure and vascular function and structure of small arteries as well as on the reactivity of the aorta in N(omega)-nitro-L-arginine methyl ester (L-NAME)-induced hypertension. Six-week-old Wistar-Kyoto rats were randomly treated for 6 weeks with placebo (control), L-NAME (70 mg/kg per day), or L-NAME plus bosentan (100 mg/kg per day). The treatments were stopped 2 to 3 days before the in vitro experiments so that only the long-term effects of the drugs could be observed. L-NAME increased systolic blood pressure: bosentan did not prevent this effect although the initial blood pressure rise was delayed (P=NS versus L-NAME group). Bosentan administration did not modify the structural alteration of the resistance vessels induced by L-NAME, nor did it improve endothelium-dependent relaxation of resistance vessels or the aorta. However, bosentan therapy markedly increased endothelium-dependent contraction to acetylcholine, which was slightly enhanced by L-NAME. In contrast, bosentan inhibited aortic endothelium-dependent contractions when applied acutely in vitro. This observation, together with the increased maximal vasoconstriction to the thromboxane A2 receptor agonist U46619 after 2 weeks of bosentan administration, suggests that bosentan also interacts with the receptors mediating endothelium-dependent contractions. In conclusion, our experiments suggest a minor role of endothelin in chronic L-NAME-induced hypertension as well as in the concomitant alterations of vascular structure.

Authors+Show Affiliations

University Hospital, Bern, Switzerland.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

9052893

Citation

Moreau, P, et al. "Blood Pressure and Vascular Effects of Endothelin Blockade in Chronic Nitric Oxide-deficient Hypertension." Hypertension (Dallas, Tex. : 1979), vol. 29, no. 3, 1997, pp. 763-9.
Moreau P, Takase H, Küng CF, et al. Blood pressure and vascular effects of endothelin blockade in chronic nitric oxide-deficient hypertension. Hypertension. 1997;29(3):763-9.
Moreau, P., Takase, H., Küng, C. F., Shaw, S., & Lüscher, T. F. (1997). Blood pressure and vascular effects of endothelin blockade in chronic nitric oxide-deficient hypertension. Hypertension (Dallas, Tex. : 1979), 29(3), 763-9.
Moreau P, et al. Blood Pressure and Vascular Effects of Endothelin Blockade in Chronic Nitric Oxide-deficient Hypertension. Hypertension. 1997;29(3):763-9. PubMed PMID: 9052893.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Blood pressure and vascular effects of endothelin blockade in chronic nitric oxide-deficient hypertension. AU - Moreau,P, AU - Takase,H, AU - Küng,C F, AU - Shaw,S, AU - Lüscher,T F, PY - 1997/3/1/pubmed PY - 1997/3/1/medline PY - 1997/3/1/entrez SP - 763 EP - 9 JF - Hypertension (Dallas, Tex. : 1979) JO - Hypertension VL - 29 IS - 3 N2 - Because nitric oxide inhibits the synthesis and vasoconstrictor effect of endothelin-1, the effect of endothelin-1 may be enhanced under conditions of chronic inhibition of nitric oxide synthesis. We studied the effect of chronic therapy with bosentan, a combined endothelin-A/endothelin-B receptor antagonist, on blood pressure and vascular function and structure of small arteries as well as on the reactivity of the aorta in N(omega)-nitro-L-arginine methyl ester (L-NAME)-induced hypertension. Six-week-old Wistar-Kyoto rats were randomly treated for 6 weeks with placebo (control), L-NAME (70 mg/kg per day), or L-NAME plus bosentan (100 mg/kg per day). The treatments were stopped 2 to 3 days before the in vitro experiments so that only the long-term effects of the drugs could be observed. L-NAME increased systolic blood pressure: bosentan did not prevent this effect although the initial blood pressure rise was delayed (P=NS versus L-NAME group). Bosentan administration did not modify the structural alteration of the resistance vessels induced by L-NAME, nor did it improve endothelium-dependent relaxation of resistance vessels or the aorta. However, bosentan therapy markedly increased endothelium-dependent contraction to acetylcholine, which was slightly enhanced by L-NAME. In contrast, bosentan inhibited aortic endothelium-dependent contractions when applied acutely in vitro. This observation, together with the increased maximal vasoconstriction to the thromboxane A2 receptor agonist U46619 after 2 weeks of bosentan administration, suggests that bosentan also interacts with the receptors mediating endothelium-dependent contractions. In conclusion, our experiments suggest a minor role of endothelin in chronic L-NAME-induced hypertension as well as in the concomitant alterations of vascular structure. SN - 0194-911X UR - https://www.unboundmedicine.com/medline/citation/9052893/Blood_pressure_and_vascular_effects_of_endothelin_blockade_in_chronic_nitric_oxide_deficient_hypertension_ L2 - https://www.ahajournals.org/doi/10.1161/01.hyp.29.3.763?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -