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 angiotensin II subtype 1 receptor antagonist losartan (both at 10 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, heart rate and heart weight were determined and experiments were conducted to assess changes in vascular reactivity and arterial medial thickness in ring segments of aorta and tail artery at the end of the treatment 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 effect 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 thickness and heart weight was seen only in losartan-treated rats. Whereas no changes in vascular reactivity were seen in hypertensive rats receiving hydralazine, norepinephrine- and serotonin-induced contractions were attenuated and acetylcholine-induced relaxations were enhanced in the losartan-treated rats. These data demonstrate that, although short-term 2-week treatment with either hydralazine or losartan results in normalization of blood pressure, only losartan resulted in significant alterations in vascular function and structure in spontaneously hypertensive rats.(ABSTRACT TRUNCATED AT 250 WORDS)
Soltis
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Division of Pharmacology and Experimental Therapeutics, College of Pharmacy, University of Kentucky, Lexington.
D000804:Angiotensin II / Q000037:antagonists & inhibitors* / Q000502:physiology; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D001713:Biphenyl Compounds / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D006830:Hydralazine / Q000494:pharmacology; D006973:Hypertension / Q000473:pathology / Q000503:physiopathology*; D007093:Imidazoles / Q000494:pharmacology*; D019808:Losartan; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000473:pathology; D051381:Rats; D011918:Rats, Inbred SHR; D013777:Tetrazoles / Q000494:pharmacology*; D014661:Vasoconstriction / Q000187:drug effects
D057911:Angiotensin Receptor Antagonists; D001713:Biphenyl Compounds; D007093:Imidazoles; D013777:Tetrazoles; D000804:Angiotensin II; D006830:Hydralazine; D019808:Losartan