Blood pressure lowering effects

Apart from possible clinical differences between the P-block-ers approved for HF, selection of a p-blocker may also be affected by pharmacologic differences. Carvedilol exhibits a more pronounced blood pressure lowering effect and thus causes more frequent dizziness and hypotension as a consequence of its ar receptor blocking activity. Therefore, in patients predisposed to symptomatic hypotension, such as those with advanced LV dysfunction (LVEF less than 20%) who normally exhibit low systolic blood pressures, metoprolol succinate may be the most desirable first-line P-blocker. In patients with uncontrolled hypertension, carvedilol may provide additional antihypertensive efficacy. 

Atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and C-type natriuretic peptide (CNP) are members of a family of so-called natriuretic peptides, synthesized predominantly in the cardiac atrium, ventricle, and vascular endothelial cells, respectively (G13, Y2). ANP is a 28-amino-acid polypeptide hormone released into the circulation in response to atrial stretch (L3). ANP acts (Fig. 8) on the kidney to increase sodium excretion and glomerular filtration rate (GFR), to antagonize renal vasoconstriction, and to inhibit renin secretion (Ml). In the cardiovascular system, ANP antagonizes vasoconstriction and shifts fluid from the intravascular to the interstitial compartment (G14). In the adrenal cortex, ANP is a powerful inhibitor of aldosterone synthesis (E6, N3). At the hypothalamic level, ANP inhibits vasopressin secretion (S3). It has been shown that some of the effects of ANP are mediated via a newly discovered hormone, called adreno-medullin, controlling fluid and electrolyte homeostasis (S8). The diuretic and blood pressure-lowering effect of ANP may be partially due to adrenomedullin (V5). 

Recent experiments carried out by BOLME and coworkers (39) now raise the question of whether the receptors involved in reducing blood pressure are epinephrine receptors or noradrenaline receptors. These workers found that in rats small doses of yohimbine and piper-oxan blocked the blood pressure lowering effect of clonidine, but did not influence the clonidine-induced increase in flexor reflex activity. This effect on the reflex mechanism is possibly mediated by noradrenaline receptors which can be blocked only by higher doses of a-adrenolytic agents. HtfKFELT et al. (40) consider that epinephrine terminals possibly innervate noradrenaline cell bodies at the locus coeruleus. 

Figure 18. Significance of the position of two chlorine atoms in the phenyl ring on the blood pressure lowering effect...

Approximately 50% of an orally administered dose of a-methyldopa is absorbed from the gastrointestinal tract. Both peak plasma drug levels and maximal blood pressure-lowering effects are observed 2 to 6 hours after oral administration. A considerable amount of unchanged a-methyldopa and several conjugated and de-carboxylated metabolites can be found in the urine. 

OE216 Khayyal, M. T., M. A. el-Ghazaly, D. M. Abdallah, N. N. Nassar, S. N. Okpanyi, and M. H. Kreuter. Blood pressure lowering effect of an olive leaf extract (Olea europaea) in L-NAME induced hypertension in rats. Arzneimittelforschung 2002 52(11) 797-802. 

Ketanserin has a complex pattern of action. It is an antagonist of 5-HT2 receptors and peripheral al adrenoceptors. Although both effects might contribute to a blood pressure lowering effect, it is likely that there is also an additional central component involved. 

Diazoxide is similar chemically to the thiazide diuretics but has no diuretic activity. It is bound extensively to serum albumin and to vascular tissue. Diazoxide is partially metabolized its metabolic pathways are not well characterized. The remainder is excreted unchanged. Its half-life is approximately 24 hours, but the relationship between blood concentration and hypotensive action is not well established. The blood pressure-lowering effect after a rapid injection is established within 5 minutes and lasts for 4-12 hours. 

Seppo, L., Jauhiainen, T., Poussa, T., and Korpela, R. 2003. A fermented milk high in bioactive peptides has a blood-pressure lowering effect in hypertensive subjects. Am. J. Clin. Nutr. 77, 326-330. 

With the newest ARB, olmesartan, a comparison with starting doses of losartan 50 mg, irbesartan 150 mg, and valsartan 80 mg, in a prospective randomized trial, showed a significantly greater reduction in DBP (11.5 mmHg) with olmesartan, followed by the other three ARBs (8.2,9.9, 7.9 mmHg, respectively). Olmesartan appeared to have a greater dose-dependent blood pressure-lowering effect than irbesartan or candesartan, followed by losartan, telmisartan, and valsartan [29]. 

Let s look at just one of the many studies done with real human subjects. For three years, 841 men and women were observed for the blood pressure-lowering effects of diet. Some people restricted sodium, some cut back on calories, and others reduced both sodium and calories. The group with the greatest drop in blood pressure was that which reduced calories. People cutting back on sodium alone showed very little difference. 

Studies have indeed shown a blood pressure-lowering effect of fish oil supplementation. But dosages have been very high, to a point that one would develop fish breath and burping, thus limiting compliance. 

For many if not most men and women, following the programs and suggestions in this book will very effectively lower their blood pressure. The blood pressure-lowering effects can be similar to, if not even better than, those of potent prescription drugs when followed faithfully. 

Diuretics, particularly the thiazides, are useful antihypertensives. They cause an initial loss of sodium with a parallel contraction of the blood and extracellular fluid volume. The effect may reach 10% of total body sodium but it is not maintained. After several months of treatment, the main blood pressure lowering effect appears to reflect a reduced responsiveness of resistance vessels to endogenous... 

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