Abstract-The aortic pulse wave contour in isolated systolic hypertension often shows a prominent reflection peak, which combines with the incident wave arising from cardiac ejection so as to widen pulse pressure. We investigated the effects of an extended-release nitrate preparation and of 2 angiotensin II (AII) inhibitors (an AII receptor antagonist and an ACE inhibitor) on the aortic pulse wave contour and systemic blood pressure in hypertensive subjects with high augmentation index caused by exaggerated pulse wave reflection. Two double-blind, randomized, placebo-controlled crossover studies were carried out in a total of 16 elderly patients with systolic hypertension resistant to conventional antihypertensive therapy. In 1 study, pharmacodynamic responses to single doses of placebo, isosorbide mononitrate, eprosartan, and captopril were determined; in the other, single-dose isosorbide mononitrate and placebo were compared in subjects treated with AII inhibitors at baseline. Blood pressure was measured by sphygmomanometry and pulse wave components by applanation tonometry at the radial artery. All 3 agents were shown to decrease brachial systolic blood pressure, aortic systolic blood pressure, and aortic pulse pressure. Qualitative effects on the aortic pulse wave contour differed: augmentation index was not significantly altered by either captopril or eprosartan but was decreased (PϽ0.0001) by Ϸ50% of the placebo value with isosorbide mononitrate in both study groups. We propose that isosorbide mononitrate corrected the magnified wave reflection in systolic hypertension of these elderly patients by an effect that was distinct from that exercised by either acute or chronic AII inhibition. Key Words: angiotensin antagonist Ⅲ antihypertensive therapy Ⅲ elderly Ⅲ hypertension, arterial Ⅲ isosorbide mononitrate Ⅲ pulse wave I solated systolic hypertension (ISH) and associated widening of pulse pressure have been identified as important risk factors for cardiovascular disease in the elderly 1-4 and may persist despite the use of conventional antihypertensive drugs. 5-7 A hierarchy of clinical responses to such therapy has been reported: Calcium antagonists produced the most significant antihypertensive effect, followed by diuretics, ACE inhibitors, and -blockers. 5 A place for nitrates in this hierarchy has been surmised for more than a decade 8,9 but has not been clearly established. 10 The high pulse pressure of ISH is usually associated with the presence in the aortic pulse wave of a prominent reflection peak, long known to be nitrate-sensitive, 11 which combines with the tail of the incident peak arising from cardiac ejection to increase pulse pressure. 12,13 We showed in a previous study that the amplitude of this wave reflection, measured by applanation tonometry, could be decreased by the use of isosorbide mononitrate (ISMN) given as an adjunct to conventional combined antihypertensive therapy. 12 This effect was associated with sustained lowering of systolic blood pressure during continued once-daily admi...
L-arginine has potential value as an adjunct to ISMN in combination with antihypertensive therapy in elderly patients with systolic hypertension. However, when given with single-dose ISMN, its vasodilator activity may overlap with that of AII inhibitors. Future studies of L-arginine in conjunction with chronic continuous ISMN dosing are warranted.
randomly selected, and stratified by province, urban and non-urban area. BP was measured electronically. Interviewers recorded demographic data, medical history and drug use patterns.The prevalence of hypertension in South Africans was 10.9% for men and 13.9% for women. Of hypertension men 41% and 67% of the women respectively knew about their hypertension. Of the women 55% and 39% of the men were taking medication, while 38% of women and 26% of men had controlled BPs below 160/95 mmHg. Of the hypertensive drugs used, diuretics were 41%, centrally acting antiadrenergic agents for 22%, ACE-inhibitors for 19% and Methyldopa for 15%. Differences were found in drug utilisation patterns of patients attending the public and private health care sectors. Of the hypertensive patients using drugs, 77% knew what condition was being treated and only 41% could name at least an appropriate drug for hypertension. Those who knew the name of the drugs taken, had better BP control than those who did not.The degree of hypertension diagnoses and control is inadequate and the South African health services need to address this. The drug utilisation pattern reveals prescribing patterns that are not in line with the nationally accepted guidelines for treating hypertension. Our aim was to determine the relative efficacy of isosorbide mononitrate (ISMN) as an adjunctive therapy for patients with systolic hypertension refractory to conventional antihypertensive agents. This was addressed by two double-blind randomised trials in subgroups from a total of 16 patients with treated systolic blood pressure above 155 mmHg at entry. On each study day, the trial drug was given at 08.00 h; between 08.00 and 16.00 h, repeated measurements were made of office blood pressure, and of pulse-wave contour using percutaneous applanation tonometry to determine aortic systolic blood pressure (ASBP) and aortic pulse wave reflectance (APWR).The first trial was a single-dose crossover trial between placebo, captopril 25 mg, eprosartan 600 mg and ISMN 60 mg, each given (a week apart) on a single day as an adjunct to ongoing therapy with beta blocker/calcium antagonist/diuretic. ISMN decreased ASBP by 28 Ϯ 4 (SEM) mmHg and APWR by 17 Ϯ 3 mmHg (each PϽ 0.005) at 16.00 h, whereas the ACE inhibitor and angiotensin II receptor antagonist each had significantly smaller and less sustained effects.The second trial tested for evidence of tolerance after long-term ISMN. Patients treated for periods of 6-60 months with ISMN 60-120 mg/day as an adjunct to conventional antihypertensive therapy were studied on the day before 2 weeks substitution of ISMN by placebo, and on the first day of re-introduction of active ISMN. Both ASBP and APWR were decreased by ISMN from elevated baseline levels (PϽ 0.02); these effects were reversible by withdrawing ISMN, and were not significantly greater when ISMN was reinstated.We conclude that ISMN is a potent adjunctive agent for antihypertensive therapy, reducing ASBP and APWR in patients with refractory systolic hypertension and also exce...
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