Combination Antihypertensive Therapy: Does It Have a Role in Rational Therapy?

The pharmacological treatment of hypertension allows one to reduce substantially the risk of developing a cardiovascular complication. It appears more and more important to bring blood pressure to normal values in order to get the maximal benefit from antihypertensive therapy. Blood pressure lowering drugs make it possible to control blood pressure in about half of the patients when administered as monotherapy. The fraction of patients with a normal blood pressure can be markedly increased by combining drugs acting by different mechanisms. Low doses of antihypertensive agents are generally enough when coadministered. This helps to keep the incidence of side effects minimal and facilitates the patient's compliance with long-term treatment. Low-dose, fixed-dose combination therapy may therefore represent a valuable option not only to treat hypertensive patients unresponsive to drugs given as monotherapy, but also to initiate the treatment. Am J Hypertens 1997;10:131S-137S ©1997 American Journal of Hypertension, Lt

Plasma Angiotensin II and the Antihypertensive Action of Angiotensin-Converting Enzyme Inhibition

The measurement of immunoreactive "angiotensin II” in plasma cannot provide an accurate reflection of the efficacy of angiotensin-converting enzyme (ACE) inhibition because different angiotensin fragments interfere in all radioimmunoassays available so far. More complex methods are necessary in order to measure specifically angiotensin-(1-8)octapeptide. With such methodology it can be shown that no tolerance develops to the angiotensin II-reducing effect of ACE inhibitors after prolonged administration. Marked reduction of angiotensin II levels can be shown even in patients with primary aldosteronism. At peak blockade, the level of plasma angiotensin II is still related to circulating active renin and angiotensin I. Accordingly, because ACE inhibitors raise circulating angiotensin I in a dose-dependent fashion, this should be taken into account when dosing ACE inhibitors. The hypothesis that tissue renin-angiotensin systems play an important independent role in determining vasomotor tone is very interesting. However, any discussion on whether tissue or plasma renin determines the pharmacological effect of ACE inhibitors should be based on the simultaneous measurement of true angiotensin II in tissue and plasma under steady-state conditions. Am J Hypertens 1989;2:286-29

Dose-Response Relationships of ACE Inhibitors and Angiotensin II Blockers

It is difficult to establish dose-response relationships for ACE inhibitors in patients with hyperternion or congestive heart failure. This has led to the widely held opinion that the effects of ACE inhibitors are hardly dose dependent. The purpose of this short discussion is to demonstrate that this class of compounds, as well as the more recent angiotemin II receptor antagonists, exhibit some very clear dose-response relationships when these are evaluated in normal volunteers based on the mechanisms for which they were designed. Characterization of these dose-response curves is important in order to use these drugs at their optimol dose and to obtain the maximal therapeutic benefi

Cardiac mass in glucocorticoid-hypertensive rats with and without circulating adrenaline

There is evidence that catecholamines may promote the development of cardiac hypertrophy in hypertension. To test the hypothesis that adrenaline directly determines left ventricular mass, normotensive Wistar rats were made adrenaline-deficient by adrenalectomy and hypertensive by administration of glucocorticoid. Blood pressure, heart rate, and body weight of the adrenalectomised group were not significantly different from a glucocorticoid treated control group with intact adrenals. Heart weight was significantly lower in the adrenalectomised rats, but this difference disappeared when heart weight was adjusted for body weight. It appears therefore that the presence or absence of adrenaline does not significantly affect cardiac mass in the presence of hypertension in this animal mode

Additions to the geographical distribution of the Malagasy family Microcharmidae Lourenço 1 996 (Scorpiones: Buthoidea) and description of three new species of Microcharmus Lourenço 1 995

A more up to date biogeographic analysis of the patterns of distribution presented by the scorpions of the family Microcharmidae Lourenço 1 996 are presented. This family is revalidated here based on numerous morphological characters. This Malagasy group of scorpions is represented by two genera, Microcharmus Lourenço 1 995 and Neoprotobuthus Lourenço 2000 both endemic to the Island. The family Microcharmidae seems to be restricted to dry and wet forests formations in the northern and northwestern portions of the island. Here we describe three species new to science:Microcharmus andrei sp. n., Microcharmus antongil sp. n. and Microcharmus djangoa sp. n. The distribution of these new species seems to be restricted to the northern range of Madagascar, in habitats ranging from dry to wet forests, confirming therefore the patterns previously observed. Une analyse biogéographique à jour portant sur les schémas de distribution des scorpions de la famille des Microcharmidae Lourenço 1 996 est présentée. La famille est ici revalidée sur la base de nombreux caractères morphologiques. Ce groupe de scorpions de Madagascar est représenté par deux genres, Microcharmus Lourenço 1 995 et Neoprotobuthus Lourenço 2000 tous deux endémiques de l’île. La famille des Microcharmidaesemble avoir une distribution limitée aux formations forestières sèches et humides des parties nord et nord-ouest de l’île. Ici, nous décrivons trois espèces nouvelles pour la scienced : Microcharmus andrei sp. n., Microcharmus antongil sp. n. et Microcharmus djangoa sp. n. La distribution de ces trois nouvelles espèces semble limitée à la partie septentrionale de Madagascar, dans des habitats allant des forêts sèches à humides, ce qui confirme ainsi les schémas préalablement observés

The renin—angiotensin system in refractory heart failure: clinical, hemodynamic and hormonal effects of captopril and enalapril

Studies using a competitive inhibitor of angiotensin II (saralasin) or converting enzyme inhibitors (teprotide, captopril, enalapril) have established that the renin-angiotensin system participates in the control of vascular tone in congestive heart failure both in experimental settings and in patients. In man, the marked decrease in left ventricular filling pressure and the variable increase in stroke volume induced by renin-angiotensin blockade suggests that angiotensin II actively constricts venous as well as arteriolar vascular beds. Captopril, in doses of 25 to 150 mg p.o. TID, maintains its efficacy during chronic administration with persistent clinical and hemodynamic improvement as well as increased exercise tolerance. In our experience, enalapril, 10 mg p.o., improves cardiac function within 4 to 6 h as reflected by a 30% decrease in left ventricular filling pressure, a 28% increase in stroke volume in the face of unchanged heart rate. Clinical improvement, enhanced exercise tolerance and characteristic hormonal responses suggest that enalapril also maintains its efficacy during long-term treatment. Chronic angiotensin II converting enzyme inhibition appears to be a major advance in the treatment of patients with severe congestive heart failure, refractory to digitalis and diuretic

The Alaotra gentle lemur: Population estimation and subsequent implications

Durrell Wildlife Conservation Trust (DWCT) has conducted since 1994 several census’ on the population of the Alaotran gentle lemur to observe the development of the population in time and space

Vascular acetylcholine response during chronic NO synthase inhibition: in vivo versus in vitro

Objective: The aim of this study was to compare the response to NO-mediated vasodilators in vivo and in vitro during chronic NO synthase inhibition. Methods:NG-Nitro-l-arginine-methyl ester (l-NAME, 0.4 g/l) or vehicle was administered in the drinking water for 6 weeks to male Wistar rats weighing 220-240 g. The effect of acetylcholine and sodium nitroprusside was examined in vivo, on systemic blood pressure and heart rate and in vitro, on the precontracted isolated mesenteric artery. The in vivo response to both vasodilators was examined in awake rats monitored by an indwelling catheter in the femoral artery. Isolated segments of the third-generation mesenteric artery were examined in vitro with a Mulvany dual myograph after precontraction with noradrenaline. Results: In isolated mesenteric arteries obtained from rats chronically treated with l-NAME, the initial relaxant response to acetylcholine was significantly decreased whereas that to sodium nitroprusside was enhanced. A late acetylcholine-induced contractile response was present and abolished by indomethacin. In vivo, the hypotensive action of sodium nitroprusside was also enhanced in the l-NAME-treated rats. Acetylcholine reduced blood pressure in the l-NAME-treated hypertensive animals more than in normotensive controls, but less than in control rats infused intravenously with noradrenaline at a dose increasing their blood pressure to hypertensive levels. Conclusions: The NO-mediated vasodilation induced by acetylcholine is attenuated during chronic NO synthase inhibition, both in vivo and in vitro. The blunted hypotensive response to acetylcholine can be demonstrated only if blood pressure of control rats is acutely increased to hypertensive level

Acoustic stimulation time-locked to the beginning of sleep apnea events reduces oxygen desaturations: a pilot-study.

We aimed to determine whether bone-conducted acoustic stimulation could prematurely terminate sleep apnea events, thereby decreasing amplitude and duration of subsequent oxygen desaturation. As oxygen desaturation has been linked to cardiovascular consequences, we postulate this could be a viable therapy in some cases. Eight patients with severe Obstructive Sleep Apnea (2 women, 45 [20-68] y.o. Apnea-Hypopnea Index: 77.7 ± 22.3/h) underwent polysomnography at the Lausanne University Sleep Center. Short acoustic stimulations were administered by bone conduction every second event of sleep apnea. Sounds were remotely administered using a Dreem® headband worn by patients while undergoing nocturnal polysomnography. Amplitude (%) and duration(s) of oxygen desaturations following terminated apneas were compared to that of non-stimulated previous and subsequent events. 549 stimulations (68.6 ± 38 sounds per patient) in N1 (16.2%), N2 (69.9%), N3 (4.2%), and REM(9.6%) were conducted. Compared to the previous and subsequent non-stimulated apnea, stimulations reduced event duration by 21.4% (-3.4 ± 7.2 s, p < 0.0001) while oxygen desaturation amplitude and duration were reduced by 30.4% (mean absolute difference ± SD: -1.9 ± 2.8%, p < 0.0001), and 39.6% (-5.7 ± 9.2 s, p < 0.0001) respectively. For these variables, each patient showed a significant improvement following acoustic stimulation. Sound-associated discomfort was rated 1.14 ± 1.53 on an 8 points scale (8 = worst) and only 6.8% of emitted sounds were perceived by the patients, suggesting a well-tolerated intervention. Bone-conducted sound stimuli decreased apnea events duration as well as duration and amplitude of associated oxygen desaturations. Stimulations were well tolerated and rarely perceived by patients. This therapeutic approach deserves further investigation, with monitoring of effects on sleep quality, daytime function/sleepiness and cardiovascular parameters