Differential effect of losartan in female and male spontaneously hypertensive rats.
We demonstrated that the decreased response to acetylcholine observed in aorta of male and female spontaneously hypertensive rats is corrected after sustained (15 days) reduction of blood pressure levels by losartan. In order to verify if the same occurs in resistance vessels, vascular diameter changes induced by topical application of acetylcholine and bradykinin (endothelium-dependent vasodilators) and sodium nitroprusside (endothelium-independent vasodilator) to mesenteric arterioles studied in vivo, in situ were determined in rats treated with losartan for 24 h (acute) or 15 days (chronic). Rats that presented similar reduction (in %) of the blood pressure levels after losartan treatment were chosen. Sodium nitroprusside induced similar responses in losartan-treated and untreated male or female SHR. Whereas in female SHR, losartan corrected the diminished arteriolar response to endothelium-dependent vasodilators after acute and chronic treatment, in male SHR this correction only occurred after chronic treatment. Thus, losartan corrected the endothelial dysfunction more easily in female than in male SHR and independently of the normalization or the magnitude of the reduction of the blood pressure levels. In an attempt to explain the difference, we evaluated the losartan effect on nitric-oxide synthase (NOS) activity and angiotensin II AT1 and AT2 receptor gene expression in these animals. In male and female SHR, NOS activity and AT1 receptor expression were not altered by acute or chronic treatment. On the other hand, AT2 receptor expression was augmented only in female SHR by these treatments. Therefore, augmented AT2 receptor expression, but not alteration of NOS activity or AT1 receptor expression, might explain the difference observed.
de P Rodrigues
Stephen F
SF
Laboratory of Hypertension, Department of Pharmacology, Institute of Biomedical Sciences, University of São Paulo, Brazil.
dos Santos
Rosangela A
RA
Silva-Antonialli
Michelle M
MM
Scavone
Cristóforo
C
Nigro
Dorothy
D
Carvalho
Maria Helena C
MH
de Cássia Tostes
Rita
R
Fortes
Zuleica B
ZB
D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001160:Arterioles / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects*; D030762:Estrous Cycle; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D006728:Hormones / Q000097:blood; D006973:Hypertension / Q000188:drug therapy / Q000503:physiopathology*; D019808:Losartan / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D008643:Mesentery / Q000098:blood supply* / Q000187:drug effects; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D051381:Rats; D011918:Rats, Inbred SHR; D044140:Receptor, Angiotensin, Type 1 / Q000235:genetics; D044139:Receptor, Angiotensin, Type 2 / Q000235:genetics; D012727:Sex Characteristics; D014661:Vasoconstriction / Q000187:drug effects
D000959:Antihypertensive Agents; D006728:Hormones; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat; D019808:Losartan