Influence of age and dietary sodium on the cardiovascular and renal effects of ramipril in spontaneously hypertensive rats.
The aim of the present study was to investigate the influence of age and an increased intake of dietary sodium on the cardiovascular and renal effects of the angiotensin converting enzyme inhibitor, ramipril. Male spontaneously hypertensive rats (SHR) aged 10 and 60 weeks received either control or a high level of sodium (0.3% vs. 2.6% Na) and ramipril (2 mg/kg/day) mixed in the chow for 6 weeks. Blood pressure was measured weekly by tail-cuff method. Arterial functions were determined by measuring vascular contractile and relaxation responses of mesenteric arterial rings in vitro at the end of the study. An age-related increase in systolic blood pressure, left ventricular (LVH) and renal hypertrophy (RH) as well as proteinuria were found in SHR. The vascular relaxation to nitroprusside was impaired in aged SHR. The high sodium intake accelerated the development of hypertension only in young SHR but increased LVH and RH in both age groups. Ramipril effectively lowered blood pressure in both age groups, but decreased the LVH significantly only in young rats. Ramipril markedly improved the vascular relaxation to acetylcholine and nitroprusside only in young rats. The vascular contractile responses to noradrenaline and potassium chloride were not affected by age, sodium intake or ramipril treatment. The high sodium intake markedly attenuated the cardiovascular effects of ramipril. The high-sodium diet enhanced the urinary excretion of cyclic GMP in both age groups, while it increased urinary excretion of protein in young SHR only. In conclusion, the cardiovascular effects of ramipril were impaired with advanced age even in the presence of a control intake of sodium. A high sodium intake attenuated or even abolished the cardiovascular effects of ramipril in both young and aged SHR.
Teräväinen
T L
TL
Department of Pharmacology and Toxicology, University of Helsinki, Finland.
Mervaala
E M
EM
Pörsti
I
I
Laakso
J
J
Vapaatalo
H
H
Karppanen
H
H
D000109:Acetylcholine; D000375:Aging / Q000502:physiology*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D000818:Animals; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D006973:Hypertension / Q000188:drug therapy* / Q000503:physiopathology / Q000652:urine; D017379:Hypertrophy, Left Ventricular / Q000503:physiopathology; D066298:In Vitro Techniques; D007668:Kidney / Q000187:drug effects / Q000503:physiopathology; D008297:Male; D008638:Mesenteric Arteries; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D009599:Nitroprusside; D017257:Ramipril / Q000037:antagonists & inhibitors / Q000627:therapeutic use*; D051381:Rats; D011918:Rats, Inbred SHR; D017207:Rats, Sprague-Dawley; D012982:Sodium, Dietary / Q000008:administration & dosage*; D014665:Vasodilator Agents
D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D012982:Sodium, Dietary; D014665:Vasodilator Agents; D009599:Nitroprusside; D017257:Ramipril; D000109:Acetylcholine