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End-organ involvement and calcium antagonist therapy: animal studies
1Department of Medicine, University of Melbourne, Austin Hospital, Heidelberg, Victoria, Australia.
Insights
Amlodipine, a calcium channel blocker, effectively lowers blood pressure in hypertensive rats, reducing cardiac hypertrophy and improving survival. It also protects blood vessels and the heart from damage associated with hypertension and high cholesterol.
Area of Science:
- Cardiovascular Pharmacology
- Hypertension Research
- Animal Models of Disease
Background:
- Hypertension leads to severe secondary complications like atherosclerosis, stroke, cardiac hypertrophy, and renal damage.
- Effective hypertension treatment requires addressing both blood pressure and its detrimental consequences.
- Amlodipine is a long-acting, vascular-selective calcium antagonist with potential to mitigate these secondary effects.
Purpose of the Study:
- To investigate the efficacy of amlodipine in attenuating secondary consequences of hypertension.
- To evaluate amlodipine's protective effects on vasculature and myocardium in animal models.
Main Methods:
- Stroke-prone and spontaneously hypertensive rats were treated orally with amlodipine (5-10 mg/kg/day) for 30 weeks.
- Cholesterol-fed rabbits received amlodipine (1-5 mg/kg/day) to assess vascular protection.
- Measurements included blood pressure, cardiac hypertrophy, survival rates, vascular calcium overload, lesion formation, and myocardial ischemia-induced changes.
Main Results:
- Amlodipine significantly lowered systolic blood pressure in hypertensive rats.
- Treatment reduced cardiac hypertrophy and prolonged survival in the rat models.
- In rabbits, amlodipine decreased vascular calcium overload and the incidence of atherosclerotic lesions.
- Protection against myocardial ischemia was evidenced by reduced externalization of endothelin-1 binding sites.
Conclusions:
- Amlodipine demonstrates significant antihypertensive effects, reducing secondary complications.
- The drug offers protective benefits for the vasculature and myocardium against hypertension-related damage.
- Amlodipine represents a promising therapeutic agent for managing hypertension and its associated cardiovascular risks.
Abstract:
Hypertension is a complex disease, the treatment of which should not only lower systolic and diastolic blood pressure but also attenuate the secondary consequences of the disease. These include vascular injury (including atherosclerosis), stroke, left ventricular hypertrophy, and renal damage. To establish whether the long-acting, vascular-selective calcium antagonist amlodipine attenuates some of these secondary consequences of hypertension, 5-week-old stroke-prone hypertensive and 8-week-old spontaneously hypertensive rats were treated (orally) with 5 mg/kg/day and 10 mg/kg/day amlodipine, respectively, for 30 weeks. The treatment resulted in a significant lowering of systolic blood pressure, accompanied by reduced cardiac hypertrophy and prolonged survival. Evidence for a protective effect of amlodipine on the vasculature was obtained by treating cholesterol-fed rabbits with 1-5 mg/kg/body weight/day. This resulted in a reduction in vascular Ca2+ overloading and a reduced incidence of sudanophilic lesion formation. Protection against ischemia-induced changes in the myocardium included a reduction in the ischemia-induced externalization of endothelin-1 binding sites.
