Protective Effects of Angiotensin II Interruption: Evidence for Antiinflammatory Actions

Nigel J. Dagenais, B.Sc.(Pharm.); Fakhreddin Jamali, Ph.D.


Pharmacotherapy. 2005;25(9):1213-1229. 

In This Article

Future Implications of Angiotensin II Interruption

Angiotensin II is now recognized as a proinflammatory agent with various implications for cardiovascular disease progression and development. Although the benefit of angiotensin II suppression in heart failure and diabetes is well established, further randomized prospective studies are needed to confirm the available data regarding cardiovascular disease. If the results are confirmed, ACE inhibitors and ARBs may represent a novel therapy for preventing cardiovascular events.

It would be interesting to assess angiotensin II suppression treatment on a long-term basis in clinical trials with young, healthy individuals to determine whether atherosclerosis could be prevented. The ACE inhibitors and ARBs are generally well tolerated and relatively inexpensive. Thus, since heart disease is the leading cause of death in the developed world, angiotensin II suppression could be a valuable adjunctive prophylactic therapy along with other interventions, such as regular exercise, healthy diet, and weight control.

Data suggest that angiotensin II disruption not only is relevant to cardiovascular disease, but also may have some benefit for patients with inflammatory disease, such as rheumatoid arthritis. Although angiotensin II interruption will probably never replace antirheumatic treatments like methotrexate and anticytokine therapies, ACE inhibitors or ARBs may act as effective adjunctive therapy for disease control in patients with rheumatoid arthritis. In addition, cardiovascular disease is highly prevalent in patients with rheumatoid arthritis, and risk of a cardiac event is elevated.[170] Since AT1 receptors apparently are not downregulated in patients with rheumatoid arthritis but may be upregulated,[121] angiotensin II disruption may play dual roles in symptom control and improved mortality. Nevertheless, large, randomized, prospective, placebo-controlled studies are needed to confirm any antiinflammatory actions of angiotensin II suppression in patients with rheumatoid arthritis.

Finally, ACE inhibitors and ARBs may represent a therapeutic modality for transplant recipients and patients with conditions such as asthma and cancer. However, most evidence suggesting a benefit from angiotensin II disruption in patients with these conditions is limited to animal research, retrospective studies, and small placebo-controlled trials. Therefore, further evidence is required to confirm these promising results in large, prospective, randomized, placebo-controlled studies.