Effects of chronic blockade of angiotensin II receptor on the maintenance of hypertension and vascular changes in spontaneously hypertensive rats.
Previous studies have shown that chronic treatment of spontaneously hypertensive rats (SHR) with angiotensin converting enzyme inhibitors is effective in causing the regression of hypertension and vascular structural changes in adult SHR. The purpose of this study was to determine the involvement of angiotensin type 1 receptors in the maintenance of hypertension and vascular changes in adult SHR. Three groups of 15-week-old male SHR were treated with three different doses of the angiotensin type 1 receptor antagonist L-158,809. After 12 weeks of treatment, average systolic blood pressure was reduced in a dose-dependent manner from 206 +/- 2 mmHg (1 mmHg = 133.3 Pa) in the control SHR to 154 +/- 7 mmHg in the 0.6 mg/kg group, 172 +/- 3 mmHg in the 0.3 mg/kg group, and 196 +/- 8 mmHg in the 0.1 mg/kg group. Withdrawal of the treatment caused a rapid rise in blood pressure within 1 week, and 14-16 weeks after treatment had been withdrawn, blood pressure of SHR treated with the highest dose had increased to 169 +/- 8 mmHg. Blood pressure of the SHR treated with the two lower doses had increased to the level of the untreated SHR. Mean blood pressure, diastolic pressure, and pulse pressure were significantly reduced in the SHR treated with 0.6 mg/kg L-158,809. The arterial media cross-sectional area and media to lumen ratio were reduced by L-158,809 treatment (0.6 mg/kg dose). Treatment did not affect body weight or heart rate. Contractile response of the mesenteric arteries to nerve or norepinephrine stimulation was not affected by the treatment. However, arteries from treated SHR did not show an angiotensin II potentiation of nerve-stimulated response, as was observed in the control SHR. We conclude that persistent control of blood pressure by treatment with L-158,809 is associated with its effects on the structure and function of the arteries in the SHR.
Gillies
L K
LK
Smooth Muscle Research Programme, McMaster University, Hamilton, ON, Canada.
Lee
R M
RM
D000367:Age Factors; D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D001835:Body Weight / Q000187:drug effects; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects*; D051381:Rats; D011918:Rats, Inbred SHR; D011945:Receptors, Angiotensin / Q000187:drug effects*
D011945:Receptors, Angiotensin; D000804:Angiotensin II