Blockade of angiotensin II provides additional benefits in hypertension- and ageing-related cardiac and vascular dysfunctions beyond its blood pressure-lowering effects.
OBJECTIVE
To assess the blockade of the renin-angiotensin system (RAS) or blood pressure-lowering on cardiovascular functions in hypertensive and ageing animals.


METHODS
Male spontaneously hypertensive rats (SHR) and their normotensive counterparts, Wistar-Kyoto rats (WKY), at the ages of 3-4 (young), 34-35 (adult) and 74-75 (old) weeks were treated with an angiotensin II type 1 receptor antagonist, losartan (25 mg/kg) or a combination of a smooth muscle relaxant and a diuretic [H/H, hydralazine (50 mg/kg) plus hydrochlorothiazide (7.5 mg/kg), respectively] for 8 weeks. Each experimental group contained 10 SHR and 10 WKY, where equal numbers of untreated animals served as controls.


RESULTS
Compared to age-matched WKY groups, SHR groups possessed, on average, 48 +/- 7 mmHg and 57 +/- 16 mmHg (P < 0.05) higher systolic blood pressure and left ventricular developed pressures, respectively. The values of these parameters were significantly lowered in both strains by both treatment regimens. SHR had higher heart rates, which were increased by H/H treatment selectively in adult and old animal groups of both strains. Both treatment regimens enhanced KCl-mediated, that is, receptor-independent, aortic contractile responses and bradykinin-mediated coronary vasodilatation in adult and old WKY and SHR age-groups. Although both therapies augmented endothelium-dependent and endothelium-independent relaxant responses in young and adult, but not in old, SHR aortas to the levels observed in age-matched WKY, these beneficial effects were more prominent with losartan. Moreover, losartan reduced heart to body weight ratio in all SHR age groups, and selectively in the old WKY group.


CONCLUSIONS
Blockade of RAS provides a better protective effect on cardiovascular function compared to sole reduction of blood pressure, and the efficacy of antihypertensive treatment is dictated by age and the hypertensive stage of the animals.
Demirci
Buket
B
Department of Medicine, Institute of Clinical Science Block B, Queen's University Belfast, Belfast, UK.
McKeown
Pascal P
PP
Bayraktutan
Ulvi
U
D000375:Aging / Q000502:physiology; D047228:Angiotensin II Type 1 Receptor Blockers / Q000008:administration & dosage*; D000818:Animals; D000959:Antihypertensive Agents / Q000008:administration & dosage; D001013:Aorta, Thoracic / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D003331:Coronary Vessels / Q000187:drug effects; D006830:Hydralazine / Q000008:administration & dosage; D006852:Hydrochlorothiazide / Q000008:administration & dosage; D006973:Hypertension / Q000188:drug therapy* / Q000503:physiopathology; D066298:In Vitro Techniques; D019808:Losartan / Q000008:administration & dosage*; D008297:Male; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D049993:Sodium Chloride Symporter Inhibitors / Q000008:administration & dosage; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000008:administration & dosage
D047228:Angiotensin II Type 1 Receptor Blockers; D000959:Antihypertensive Agents; D049993:Sodium Chloride Symporter Inhibitors; D014665:Vasodilator Agents; D006852:Hydrochlorothiazide; D006830:Hydralazine; D019808:Losartan