Blood pressure, controlling, effectiveness

Although blood pressure control follows Ohm s law and seems to be simple, it underlies a complex circuit of interrelated systems. Hence, numerous physiologic systems that have pleiotropic effects and interact in complex fashion have been found to modulate blood pressure. Because of their number and complexity it is beyond the scope of the current account to cover all mechanisms and feedback circuits involved in blood pressure control. Rather, an overview of the clinically most relevant ones is presented. These systems include the heart, the blood vessels, the extracellular volume, the kidneys, the nervous system, a variety of humoral factors, and molecular events at the cellular level. They are intertwined to maintain adequate tissue perfusion and nutrition. Normal blood pressure control can be related to cardiac output and the total peripheral resistance. The stroke volume and the heart rate determine cardiac output. Each cycle of cardiac contraction propels a bolus of about 70 ml blood into the systemic arterial system. As one example of the interaction of these multiple systems, the stroke volume is dependent in part on intravascular volume regulated by the kidneys as well as on myocardial contractility. The latter is, in turn, a complex function involving sympathetic and parasympathetic control of heart rate intrinsic activity of the cardiac conduction system complex membrane transport and cellular events requiring influx of calcium, which lead to myocardial fibre shortening and relaxation and affects the humoral substances (e.g., catecholamines) in stimulation heart rate and myocardial fibre tension. 

The therapeutic effect is achieved and blood pressure controlled. 

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). 

The Rauwolfia alkaloid reserpine, due to its strong central component of activity, is excluded from this review, even though it has the peripheral effect of releasing norepinephrine from storage sites where it can be metabolized by monoamine oxidase. This results in neurotransmitter depletion and it appears that good blood pressure control would be achieved by a drug which has this peripheral mechanism but lacks the central component. The Mead-Johnson compound MJ-10459-2 (LXI) shows activity in... 

A 5 year randomized clinical trial in the United States found that in spite of the availability of hypertensive medication, awareness promotions, and guidelines, only a third of all the hypertensive patients have their blood pressure under effective control due to noncompUance in medication. More tailored behavioral management intervention may help to improve compliance and achieve better control. 

Tolerance Tolerance may occur, usually between the second and third month of therapy. Adding a diuretic or increasing the dosage of methyidopa frequently restores blood pressure control. A thiazide is recommended if therapy was not started with a thiazide or if effective control of blood pressure cannot be maintained on 2 g methyidopa daily. 

Klahr S, Levey AS, Beck GJ, Caggiula AW, Hunsicker L, Kusek HW et al. The effects of dietary protein restriction and blood-pressure control on the progression of chronic renal disease. Modification of diet in Renal Disease Study Group. N Engl J Med 1994 330 877-84. 

Type B effects are rare but should be recognized. They include oedema of the lower limbs (bromocriptine, amantadine), livedo reticularis (amantadine), diarrhoea (tolcapone, entacapone), paroxysmal hypertension and dysregulation of blood pressure control (selegiline), narcoleptic phenomena (pramipex-ole), and insomnia (all dopaminergic agonists). 

Ginkgo may reduce the effectiveness of thiazide diuretics for blood pressure control and at least theoretically should be avoided with MAOIs. There is also a suggestion that ginkgo may decrease male and female fertility, and it should be avoided in those trying to conceive. 

Clonidine is lipid-soluble and rapidly enters the brain from the circulation. Because of its relatively short half-life and the fact that its antihypertensive effect is directly related to blood concentration, oral clonidine must be given twice a day (or as a patch, below) to maintain smooth blood pressure control. However, as is not the case with methyldopa, the dose-response curve of clonidine is such that increasing doses are more effective (but also more toxic). 

Appel LJ et al Effects of comprehensive lifestyle modification on blood pressure control Main results of the PREMIER clinical trial. JAMA 2003 289 2083.[PMID 12709466]... 

Tannen, R. L. 1983. Effects of potassium on blood pressure control. Ann. Intern. Med. 98(Part 2), 773-780. 

The clinical manifestations of PAD are associated with reduction in functional capacity and quality of life, but because of the systemic nature of the atherosclerotic process there is a strong association with coronary and carotid artery disease. Consequently, patients with PAD have an increased risk of cardiovascular and cerebrovascular ischemic events [myocardial infarction (Ml), ischemic stroke, and death] compared to the general population (4,5). In addition, these cardiovascular ischemic events are more frequent than ischemic limb events in any lower extremity PAD cohort, whether individuals present without symptoms or with atypical leg pain, classic claudication, or critical limb ischemia (6). Therefore, aggressive treatment of known risk factors for progression of atherosclerosis is warranted. In addition to tobacco cessation, encouragement of daily exercise and use of a low cholesterol, low salt diet, PAD patients should be offered therapies to reduce lipid levels, control blood pressure, control blood glucose in patients with diabetes mellitus, and offer other effective antiatherosclerotic strategies. A recent position paper... 

Diabetes is the most frequent cause of end-stage renal disease. Hypertension, which is common among patients with type 2 diabetes, accelerates the development and progression of renal disease. Early and tight blood pressure control in diabetic patients, preferably with antihypertensive agents that have proven reno-protective properties, is therefore essential to minimize loss of kidney function. Several controlled clinical trials have investigated and proved the beneficial effects of ARBs on type 2 diabetic nephropathy [10-14]. 

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