Study Hypertension

W. B. Kaimel and T. R. Dauber, Hypertensive Cardiovascular Disease The Framingham Study. Hypertension Mechanisms and Management, Framingham, Mass., 1973. 

As a result of such studies hypertension has been operationally defined as the blood pressure level above which therapeutic intervention has clinical benefit. As increasingly aggressive intervention has continued to demonstrate benefits, this level has gradually reduced over time and is commonly defined as systolic blood pressure>l40 mmHg and/or diastolic blood pressure >90 mmHg (Table 1). Isolated systolic hypertension is defined as systolic blood pressure >140 mmHg and diastolic blood pressure <90 mmHg. 

Sethi AA, Nordestgaard BG, Ager-holm-Larsen B, Frandsen E, Jensen G, Tybjaerg-Hansen A. Angiotensinogen polymorphisms and elevated blood pressure in the general population - the Copenhagen City Heart study. Hypertension 2001 37 875-881. 

Van Dijk EJ, Breteler MM, Schmidt R, Berger K, Nilsson LG, Oudkerk M, Pajak A, Sans S, de Ridder M, Dufouil C, Fuhrer R, Giampaoli S, Launer LJ, Hofman A CASCADE Consortium (2004) The association between blood pressure, hypertension, and cerebral white matter lesions cardiovascular determinants of dementia study. Hypertension 44 625-630... 

Glorioso N, Manunta P, EiUgheddu F, et al. The role of alpha-adducin polymorphism in blood presstrre and sodium handling regulation may not be excluded by a negative association study. Hypertension 1999 34 649-654. 

Fuchs FD, Ch bless LE, Whelton PK, Nieto FJ, Heiss G. Alcohol consumption andtiie incidence of hypertension. The Atherosclerosis Risk in Communities Study. Hypertension (2001)37, 1242-50. 

Iwata, S., et al. Higher Ambulatory Blood Pressure Is Associated With Aortic Valve Calcification in the Elderly A Population-Based Study. Hypertension 61(1), 55-60 (2013)... 

Zhang, Y, Lee, E.T., Devereux, R.B. et al. 2006. Prehypertension, diabetes, and cardiovascular disease risk in a population based sample The strong heart study. Hypertension 47 410-414. 

Lankhorst S, Baelde HI, Kappers MH et al (2015) Greater sensitivity of blood pressure than renal toxicity to tyrosine kinase receptor inhibition with sunitinib. Hypertension 66 543-549 Lankhorst S, Kappers MH, van Esch JH et al (2014) Treatment of hypertension and renal injury induced by the angiogenesis inhibitor sunitinib precUnical study. Hypertension 64 1282-1289 Le DL, Cao H, Yang LX (2014) Cardiotoxicity of molecular-targeted drug therapy. Anticancer Res 34 3243-3249... 

Dustan HP (1990) Irvine Page lecture. Legacies of Irvine H. Page. J Hypertens Suppl 8 S29-S34 Franklin SS, Thijs L, Hansen TW et al (2013) White-coat hypertension new insights from recent studies. Hypertension 62 982-987... 

The attempts to reproduce experimentally the syndrome essentially similar to hypertension led to the discovery of the renal hypertensin (226,585). Various stimuli, whether physiological or not, provoke the liberation from the renal cortex, of a protein called renin, which has been extracted (414) and partially purified (508). Renin is an enzyme which reacts with a pseudoglobulin in the serum, hypertensinogen, to produce a peptide, hypertensin or angiotonin, which has certain vasoconstrictive and hypertensive properties. In publications by Schales (509) and Corcoran (139), numerous details on renin and its characteristics are found, and Corcoran et al. (140) have recently studied hypertension. 

Bopindolol is a long-acting, nonselective P-adrenoceptor blocker. It has mild membrane stabilizing activity and ISA. In vivo, the compound is hydrolyzed to its active metabohte. Because of this prodmg feature the onset of action is slower than other available P-adrenoceptor blockers. Preliminary pharmacokinetic studies indicate that the compound is weU absorbed, is 70% bioavailable, and peak plasma levels are achieved in about 2 h. Whereas its elimination half-life is 4—8 h, P-adrenoceptor blocking action (- 40%) is stiU apparent after 48 h. The dmg is being studied in hypertension, angina, and arrhythmias (43). 

Bisoprolol fumarate is a long-acting, cardioselective -adrenoceptor blocker, and is the most potent cardioselective -adrenoceptor blocker available. Bisoprolol has no ISA. At high concentrations it has membrane-stabilizing activity. The dmg has a "balanced clearance", ie, half is excreted by the kidneys and half is eliminated by the Hver and its excretion is not affected by functional impairment of either organ. It is approved in Europe for hypertension and is being studied in angina (43). 

Hypokalemia. Hypokalemia associated with thia2ide diuretic therapy has been knpHcated in the increased incidence of cardiac arrhythmias and sudden death (82). Several large clinical trials have been conducted in which the effects of antihypertensive dmg therapy on the incidence of cardiovascular complications were studied. The antihypertensive regimen included diuretic therapy as the first dmg in a stepped care (SC) approach to lowering the blood pressure of hypertensive patients. 

One study (83) indicated that in mildly hypertensive male patients treated with an antihypertensive dmg, those below the age of 50 or having no clinical evidence of cardiovascular disease had no significant improvement from cardiovascular diseases within 3.3 years those over the age of 50 or having pre-existing cardiovascular disease benefited significantly. 

Another study (84), which enrolled men and women between the ages of 21—55 who had mild hypertension and no recognizable cardiovascular risk factors, showed no significant differences in mortaUty between dmg- and placebo-treated patients. Significant reductions in hypertensive complications were noted, but atherosclerotic complications were not reduced. 

A third study (85) enrolled 7825 hypertensive patients (55% males and 45% females) having diastoHc blood pressures (DBP) of 99—104 mm Hg (13—14 Pa) there were no placebo controls. Forty-six percent of the patients were assigned to SC antihypertensive dmg therapy, ie, step 1, chlorthaUdone step 2, reserpine [50-55-5] or methyldopa [555-30-6], and step 3, hydralazine [86-54-4]. Fifty-four percent of the patients were assigned to the usual care (UC) sources in the community. Significant reductions in DBP and in cardiovascular and noncardiovascular deaths were noted in both groups. In the SC group, deaths from ischemic heart disease increased 9%, and deaths from coronary heart disease (CHD) and acute myocardial infarctions were reduced 20 and 46%, respectively. 

Medical researchers studying high blood pressure have consistently found that people with hypertension have high blood levels of some sort of Na, K -... 

ATPase inhibitor. In such patients, inhibition of the sodium pump in the cells lining the blood vessel wall results in accumulation of sodium and calcium in these cells and the narrowing of the vessels to create hypertension. An 8-year study aimed at the isolation and identification of the agent responsible for these effects by researchers at the University of Maryland Medical School and the Upjohn Laboratories in Michigan recently yielded a surprising result. Mass spectrometric analysis of compounds isolated from many hundreds of gallons of blood plasma has revealed that the hypertensive agent is ouabain itself or a closely related molecule ... 

Dr. Kenneth Mukamal sfindings were published in January 2003. The news just gets better. A study whose Jindings were released in March 2004 suggested that moderate drinking not only had protective cardiovascular effects, but that it was also protective for people with hypertension. 

ACE inhibitors are approved for the treatment of hypertension and cardiac failure [5]. For cardiac failure, many studies have demonstrated increased survival rates independently of the initial degree of failure. They effectively decrease work load of the heart as well as cardiac hypertrophy and relieve the patients symptoms. In contrast to previous assumptions, ACE inhibitors do not inhibit aldosterone production on a long-term scale sufficiently. Correspondingly, additional inhibition of aldosterone effects significantly reduces cardiac failure and increases survival even further in patients already receiving diuretics and ACE inhibitors. This can be achieved by coadministration of spironolactone, which inhibits binding of aldosterone to its receptor. 

BAYK8644 is a DHP with Ca2+ channel activating properties. Although some therapeutic effects can be envisaged for such drugs (such as stimulation of glucose-dependent insulin secretion, positive inotropy), severe side effects are also predicted from animal studies (dystonic neurobehavioral syndrome, hypertension, arrhythmias), which currently prevents their clinical development. 

If 50% of Europeans with essential hypertension are affected by this disease because of an elevated secretion of endogenous ouabain, then there might be a chance to block its interaction at the cardiac glycoside binding site of Na+/K+-ATPase and thus lower blood pressure. This therapeutic approach seems to be successfiil. Recent studies provide evidence that the cardenolide analogue Rostafuroxin (PST 2238 Fig. 4) at very low concentrations can overcome the ouabain-induced tise of hypertension in experimental animals [6]. This compound has recently entered the phase I of clinical trials and is certainly a prototype of a new class of antihypertensive drugs. 

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