ALTERATIONS IN VASCULAR STRUCTURE AND FUNCTION AFTER SHORT-TERM LOSARTAN TREATMENT IN SPONTANEOUSLY HYPERTENSIVE RATS

The current study was performed to investigate the effects of a 2-week treatment regimen with either hydralazine or the nonpeptide angiotens in II subtype 1 receptor antagonist losartan (both at 1 0 mg/kg daily s.c. injection) on blood pressure and vascular smooth muscle function and structure in male spontaneously hypertensive rats with established hypertension (24 weeks of age; systolic blood pressure = 174 +/- 7 mm Hg). Systolic blood pressure and body weight were recorded before and once weekly after initiation of treatment. Mean arterial pressure, he art rate and heart weight were determined and experiments were conduct ed to assess changes in vascular reactivity and arterial medial thickn ess in ring segments of aorta and tail artery at the end of the treatm ent period. Systolic blood pressure, as well as mean arterial pressure , were significantly decreased to normotensive levels in hypertensive rats after 2 weeks of either hydralazine or losartan treatment. No eff ect on heart rate was observed in response to either antihypertensive agent. Body weight was not affected in either of the treatment groups, but a significant decrease in artery ring weight, arterial medial thi ckness and heart weight was seen only in losartan-treated rats. Wherea s no changes in vascular reactivity were seen in hypertensive rats rec eiving hydralazine, norepinephrine- and serotonin-induced contractions were attenuated and acetylcholine-induced relaxations were enhanced i n the losartan-treated rats. These data demonstrate that, although sho rt-term 2-week treatment with either hydralazine or losartan results i n normalization of blood pressure, only losartan resulted in significa nt alterations in vascular function and structure in spontaneously hyp ertensive rats. The observations support the hypothesis that angiotens in 11 plays a significant role in the maintenance of hypertension and cardiovascular hypertrophy in this model.