Cardioprotective effect

Patients having high plasma renin activity (PRA) (>8 ng/(mLh)) respond best to an ACE inhibitor or a -adrenoceptor blocker those having low PRA (<1 ng/(mLh)) usually elderly and black, respond best to a calcium channel blocker or a diuretic (184). -Adrenoceptor blockers should not be used in patients who have diabetes, asthma, bradycardia, or peripheral vascular diseases. The thiazide-type diuretics (qv) should be used with caution in patients having diabetes. Likewise, -adrenoceptor blockers should not be combined with verapamil or diltiazem because these dmgs slow the atrioventricular nodal conduction in the heart. Calcium channel blockers are preferred in patients having coronary insufficiency diseases because of the cardioprotective effects of these dmgs. 

Mitochondria KATP channels Cardiac KATP channel opening has a role in myocardial preconditioning, a paradoxical form of cardioprotection wherein brief ischemic episodes can protect the heart from subsequent lethal ischemic injury. Openers including BMS-180448 and BMS-191095 have been reported to possess preferential cardioprotective effects over vasorelaxant effects by activating mitochondria KAXP channels. 

Mortality rates from CVD are generally lower in Asian populations compared to Western populations (Knight and Eden, 1996). Although many dietary factors are known to play a protective role in CVD and it has been suggested that phytoestrogen content of Asian diets may be responsible for the cardioprotective effect. 

Recently, the possible synergistic interaction between flavonoids has been thoroughly discussed in connection with the cardioprotective effect of red wine and purple grape juice. 

In epidemiologic studies, ingestion of large amounts of cold-water oily fish was associated with a reduction in CHD risk. Fish oil supplementation has a fairly large effect in reducing triglycerides and VLDL cholesterol, but it either has no effect on total and LDL cholesterol or may cause elevations in these fractions. Other actions of fish oil may account for any cardioprotective effects. 

Resveratrol has a long history. It was initially isolated from the roots of white hellebore in 1940. No one paid much attention. In 1963, it was isolated from a plant used for centuries in traditional Japanese and Chinese medicine. Again, this did not attract much attention. The story got a lot hotter in 1992 when the presence of resveratrol in red wine was suggested to be associated with the cardioprotective effects of red wine. 

Estrogens only (oral) Evidence of the carcinogenic (breast and endometrial cancers) potential of these agents and lack of cardioprotective effect in older women. Low... 

Cook, N.C. and Samman, S., Flavonoids — chemistry, metabolism, cardioprotective effects, and dietary sources, J. Nutr. Biochem., 7, 66, 1996. 

Estrogen administration in postmenopausal women has been observed to produce cardioprotective benefits. The exact biomolecular mechanisms for this cardioprotection are unclear but it is likely that actions mediated both through the estrogen receptors, such as the beneficial alteration in lipid profiles and upregulation of the low-density lipoprotein (LDL) receptor, and independently of the estrogen receptors, such as antioxidant action, contribute to the observed cardioprotective effects of estrogens. 

Lower incidence of heart disease has also been reported in populations consuming large amounts of soy products. Lowering of cholesterol is probably the best-documented cardioprotective effect of soy. ° Soy protein incorporated into a low-fat diet can reduce cholesterol and LDL-cholesterol concentrations and the soy isoflavones are likely to contribute to these effects. Soy isoflavones have been reported to improve cardiovascular risk factors in peripubertal rhesus monkeys, and inflammatory markers in atherosclerotic, ovariecto-mized monkeys. The potential role of phytoestrogens, including isoflavonoids, as cardioprotective agents has been extensively reviewed." ... 

In contrast to the adverse physiologies associated with bradykinin release, there is a growing body of literature that implicates bradykinin as a protective agent during periods of cardiac or renal stress [14-16]. In this regard there is substantial evidence that the cardioprotective effects afforded by ACE-inhibitor treatment are a result of metabolically preserving bradykinin and are therefore mediated by bradykinin B2 (and possibly 1) receptors [17-18]. These results point to a possible therapeutic role for a kinin receptor agonist. 

Recent evidence indicates that a dose of forty to eighty milligrams of aspirin a day is probably sufficient to bring about the cardioprotective effects. And at this dose the risk of gastric complications is veiy small. So is the risk of other complications, like the one experienced by a woman who took twelve tablets daily for her arthritis. She began to hear music, even when she... 

Selective 8 agonists have been shown to exert potent cardioprotective effects in intact animals and cardiac myocytes via activation of Gi/0 proteins, protein kinase C, and ultimately the mitochondrial Katp channel (Warltier et al., 2000 Schultz et al., 2001). 

Furthermore, polyphenolics present in wine, of which flavonoids are important components, have been suggested to be responsible of the so called French paradox, that is, the unexpectedly low rate of mortality from coronary heart disease in French population despite an unfavourable exposure to known cardiovascular risk factors such as high saturated fat consumption [19-21]. Epidemiological studies in USA [22] and Denmark [23] reported that moderate red wine drinkers had a lower risk of coronary artery disease than participants with no alcoholic beverage preference. However, controversial results about the antioxidant capacity of human serum after red wine consumption have been reported [24-27]. It is therefore uncertain whether wine constituents other than alcohol add to the cardioprotective effects of red wine. 

Palmer TM, Stiles GL (2000) Identification of threonine residues controlling the agonist-dependent phosphorylation and desensitization of the rat A3 adenosine receptor. Mol Pharmacol 57 539-545 Parsons M, Young L, Lee JE, Jacobson KA, Liang BT (2000) Distinct cardioprotective effects of adenosine mediated by differential coupling of receptor subtypes to phospholipases C and D. FASEB J 14 1423-1431... 

Rose Meyer RB, Hope W (1990) Evidence that A2 purinoceptors are involved in endothelium-dependent relaxation of the rat thoracic aorta. Br J Pharmacol 100(3) 576-580 Rubio R, Ceballos G (2003) Sole activation of three luminal adenosine receptor subtypes in different parts of coronary vasculature. Am J Physiol 284(1) H204-H214 Safran N, Shneyvays V, Balas N, Jacobson KA, Nawrath H, Shainberg A (2001) Cardioprotective effects of adenosine A3 and A3 receptor activation during hypoxia in isolated rat cardiac myocytes. Mol Cell Biochem 217(1-2) 143-152 Salvatore CA, Tilley SL, Latour AM, Fletcher DS, Roller BH, Jacobson MA (2000) Disruption of the A3 adenosine receptor gene in mice and its effect on stimulated inflammatory cells. J Biol Chem 275(6) 4429-4434... 

As for the cardiovascular system, the cardioprotective effects of selective H3-receptor agonists, demonstrated in models of protracted myocardial ischemia (Imamura et al., 1994, 1995, 1996a Hatta et al., 1996, 1997), could be predictive of beneficial effects in coronaropatic patients. Hence, the attenuation of carrier-mediated noradrenaline release in hypoxic and/or ischemic myocardium by H3-agonists would limit the sympathetic overactivity and the associated incidence of ventricular arrhythmias and angina, as well as the increase of metabolic demand by the myocardium, thus preventing further damage and cardiac failure. 

The effects of raloxifene on the vascular endothelium have been studied in 19 subjects who underwent endothelial function testing at baseline and after treatment with placebo or raloxifene (60 mg/day for 6 weeks) (27). The findings in this small short-term study were entirely positive. Brachial artery diameter change (flow-mediated dilatation) increased 5.0% with placebo and 8.6% with raloxifene in response to a hyperemic stimulus. The ratio of AUC response to AUC reference with the use of laser Doppler measures was 1.18 for placebo and 1.28 for raloxifene. Flow-mediated dilatation and AUC ratio correlated significantly. The authors concluded that raloxifene enhanced endothelial-mediated dilatation in brachial arteries and digital vessels in these women, and they discussed the drug s possible cardioprotective effect. 

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