Many types of bioactive peptides that inhibit angiotensin I, angiotensin I converting enzyme (ACE) and Ang II type 1 receptor (AT1) in the cardiovascular system contribute to the prevention and treatment of hypertension. These inhibitory peptides are derived from many food proteins or artificial synthetic products. Further research examining the bioavailability of ACE inhibitory peptides will lead to the development of more effective ACE inhibitory peptides and foods. Our research also demonstrates that ACE inhibitory peptide LAP may lower blood pressure with no adverse effects.
Blood pressure is controlled by a number of different interacting biochemical pathways and can be increased or decreased depending on which pathways predominates at any given time. Classically, blood pressure control has been associated with the renin-angiotensin system, which plays an important role in regulating arterial pressure [13]. Renin converts angiotensinogen from the liver to the decapeptide angiotensin I, which in turn undergoes proteolytic cleavage to the biologically active octapeptide, angiotensin II. The latter step is carried out by angiotensin converting enzyme (ACE), which is highly expressed on vascular endothelium, particularly in the lungs. ACE belongs to the class of zinc proteases that need zinc and chloride for its activation. It converts the biologically inactive angiotensin I to the potent vasoconstrictor and cardiovascular trophic factor angiotensin II [15], [35], [40]. Angiotensin II has many important actions, including: increasing arterial pressure, increasing sodium and fluid retention, enhancing sympathetic adrenergic function and causing cardiac and vascular remodeling. For the most part, these actions are mediated by the plasma membrane AT 1 and are generally opposed by the type 2 receptor (AT 2) [58]. The ability of ACE inhibitors and AT 1-receptor antagonists to influence cardiovascular status in hypertensive conditions is consistent with an important role for the renin-angiotensin system in physiological and pathophysiological states [10], [50], [99]. Thus, inhibition of this enzyme or AT 1 is believed to lower blood pressure. At present, the renin-angiotensin system has become a key target for drugs combating hypertension.
Hypertension is a significant health problem worldwide. It is one of the major controllable risk factors associated with cardiovascular disease events such as myocardial infarction, heart failure, and end-stage diabetes [12], [16], [39], [46], [70], [71], [76]. Various synthetic ACE inhibitors are widely used to treat cardiovascular disorders [35]. In the USA alone, current annual antihypertensive drug costs are approximately $15 billion [8], [21], [22], [46], [92]. Conventional antihypertensive drugs cause various adverse effects, so cheaper, safer alternatives are desirable.
Some natural or synthesized peptides which act on the renin-angiotensin system have the ability to reduce blood pressure. At present, a higher dietary protein intake seems to have a favorable influence on blood pressure in hypertensive individuals. The Dietary Approaches to Stop Hypertension trial demonstrated that a diet rich in fruits, vegetables and low-fat dairy products would reduce blood pressure effectively [4], [9], [29], [93]. Increasing consumer knowledge of the link between diet and health has raised the awareness and demand for functional food ingredients and nutraceuticals. This is leading to a mindset of self-medication often driven by the desire to avoid undesirable side effects associated with consumption of organically synthesized chemical drugs and also to avoid the increasing cost of drug therapy. It is well recognized that apart from their basic nutritional role many food proteins contain encrypted within their primary structures peptide sequences capable of modulating specific physiological functions. The application of specific foods or food components in the prevention and/or treatment of disease are of particular relevance in the management of hypertension [104]. Although other mechanisms play a role, ACE inhibition by bioactive peptides released from food proteins may cause these antihypertensive effects. Indeed, peptides which are derived from food have certain advantages. Several studies in spontaneously hypertensive rats (SHR) suggest a significant suppression of the development of hypertension with a diet rich in ACE inhibitory peptides [25], [65], [87], [89]. A number of research reports have also demonstrated the antihypertensive effect of ACE inhibitory peptides or foods containing these bioactive compounds in hypertensive patients [20]. Overall, this points to the fact that ACE inhibitory peptides, as part of a food product or as nutraceutical, may be of functional interest in both the treatment and the prevention of hypertension. ACE inhibitory peptides have lower ACE inhibitory activity in vitro than the ACE inhibitory drugs, yet do not have the harmful side effects and also lower the cost of healthcare [57], [79].
These peptides need to be considered as hypotensive agents. Increasingly, research is exploring the relation between these peptides and their antihypertensive effects. We investigate the effects on blood pressure of the angiotensin-converting enzyme inhibitory peptide LAP. This peptide decreases the systolic blood pressure (SBP) of SHR. So we review recent discoveries of these peptide functions for developing better therapeutic modalities in treating hypertension.
Check access to the full text by signing in through your organization.
The earliest reports on exogenous inhibitors of ACE displaying an antihypertensive effect in vivo were from snake venom. Thereafter, many other ACE inhibitors have been isolated from snake venom (Table 1) [18], [19]. Many ACE inhibitory peptides have been discovered [27], [38], among which some are derived from food proteins, including animal- and plant-derived peptides. ACE inhibitors have been derived from milk, corn and fish protein sources. We categorize food-derived peptides into three
All the above ACE inhibitory peptides show some common features. The construction of ACE inhibitory peptides is based on the structure–activity relationship. Their inhibitory activity is mainly dependent on a specific structure. These peptides are regarded as competitive substrates for ACE. Of course, some researchers have suggested that ACE inhibitory peptides may exert an additional antihypertensive effect by inhibition of chymase [95], [103] but here discussion is limited to the ACE pathway.
Immunomodulatory peptides may act to stimulate immune defense systems. As early as 1968, studies on the effects of passive and active immunization against angiotensins were stimulated, though passive immunization was able to cause suppression of responses to exogenous AII and AI, the effects of active immunization were variable, particularly with regard to influence on blood pressure in hypertensive models [60]. At present, the targets for immunization against renin-angiotensin system are
Copyright © 2008 Elsevier Inc. All rights reserved.
