Endothelial dysfunction in spontaneously hypertensive rats: consequences of chronic treatment with losartan or captopril.
BACKGROUND
Hypertension is associated with endothelial dysfunction characterized by decreased endothelium-dependent relaxations and increased endothelium-dependent contractions. Angiotensin converting enzyme inhibitors and thromboxane A2 receptor antagonists decreased the endothelium dysfunction in hypertensive animals.


OBJECTIVE
To investigate the effects of prolonged treatment with losartan on endothelium-dependent and -independent relaxations and contractions in aortic rings from spontaneously hypertensive rats (SHR).


METHODS
Male SHR aged 16 weeks were treated for 12 consecutive weeks either with 10 mg/kg losartan per day or with 60 mg/kg captopril per day administered via their drinking water. The systolic blood pressure was evaluated basally and during week 12. At the end of the treatment period, the vascular reactivity in aortic rings was studies. A group of rats treated with captopril was studies as a reference group.


RESULTS
Losartan and captopril reduced the blood pressure significantly and comparably. Both drugs enhanced acetylcholine-induced relaxations and reduced the maximal contractile response to acetylcholine in the presence of NG-nitro-L arginine methyl ester (L-NAME). Contractile responses to phenylephrine, endothelin-l and U46619 were not affected by these treatments. Increased relaxing responses to superoxide dismutase were observed only in captopril-treated rats. Losartan reduced the contractile response to angiotensin II. By contrast this contractile response was elevated in rats treated with captopril.


CONCLUSIONS
Prolonged antihypertensive treatments with losartan and captopril decreased the endothelial dysfunction in aortic rings from SHR not only by enhancing NO-dependent relaxations but also by reducing the contractions in response to an endothelium-derived contracting factor. The results further confirm that an endothelium-derived contracting factor plays a role in vascular dysfunction in SHR and the relationships between this factor and angiotensin II.
Rodrigo
E
E
Department of Physiology, School of Medicine, Complutense University, Madrid, Spain.
Maeso
R
R
Muñoz-García
R
R
Navarro-Cid
J
J
Ruilope
L M
LM
Cachofeiro
V
V
Lahera
V
V
D000109:Acetylcholine / Q000494:pharmacology; D000804:Angiotensin II / Q000494:pharmacology; D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use; D000818:Animals; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D001013:Aorta, Thoracic / Q000187:drug effects / Q000503:physiopathology; D001713:Biphenyl Compounds / Q000008:administration & dosage / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects; D002216:Captopril / Q000008:administration & dosage / Q000627:therapeutic use*; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000503:physiopathology*; D006973:Hypertension / Q000188:drug therapy* / Q000503:physiopathology*; D007093:Imidazoles / Q000008:administration & dosage / Q000627:therapeutic use*; D066298:In Vitro Techniques; D019808:Losartan; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D013482:Superoxide Dismutase / Q000494:pharmacology; D013777:Tetrazoles / Q000008:administration & dosage / Q000627:therapeutic use*; D014661:Vasoconstriction / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects
D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D001713:Biphenyl Compounds; D007093:Imidazoles; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D013777:Tetrazoles; D000804:Angiotensin II; D002216:Captopril; D013482:Superoxide Dismutase; D019808:Losartan; D000109:Acetylcholine; D019331:NG-Nitroarginine Methyl Ester