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Biomedical subjects

J Ménard

Publications and source records attributed to J Ménard.

At least 91 records · Page 5Linked to original sources
PubMed1994

Blood pressure effects of acute intravenous renin or oral angiotensin converting enzyme inhibition in essential hypertension.

OBJECTIVE: To assess the participation of the renin-angiotensin system in the blood pressure regulation of essential hypertensive patients through acute specific renin inhibition. DESIGN AND METHODS: Fifty-three consecutive untreated hypertensive patients (mean +/- SD age 55 +/- 10 years, 42 male) were investigated on their usual sodium diet in a 3-h protocol. The first 11 patients did not receive any drug, the following 20 patients ingested a single oral dose of captopril (1 mg/kg) and the last 22 patients received a renin inhibitor infusion (remikiren; 1 mg/kg over 60 min). RESULTS: The maximum diastolic blood pressure fall was comparable in the two treated groups. Diastolic blood pressure changes analysed as area under the curve were similar for both drugs (overall F1,40 = 1.26, P = 0.27). Even though the baseline renin levels were within the narrow range 5-80 pg/ml, the diastolic blood pressure fall analysed as area under the curve from time 32 min to time 60 min was significantly correlated with the baseline active renin level in both groups (remikiren r = 0.44, P < 0.05; captopril r = 0.47, P < 0.05). The plasma active renin levels were significantly increased at 30, 90 and 120 min in both groups, and the maximum active renin levels were significantly correlated with the baseline active renin level (remikiren r = 0.62, P < 0.01; captopril r = 0.66, P < 0.01). The plasma prorenin levels did not change. CONCLUSIONS: This study suggests that acute renin inhibition and acute angiotensin converting enzyme inhibition similarly decrease the blood pressure and increase the plasma active renin levels. Acute blockade of the renin-angiotensin system at its initial step by a renin inhibitor can therefore be used to investigate the renin dependence of the blood pressure in essential hypertension.

Administration, Oral↗
PubMed1993

[Drug aid to tobacco withdrawal].

Persistent tobacco abuse is due to a pharmacological dependence to nicotine and to a psychological dependence to smoking. Tobacco replacement therapies, i.e. nicotine chewing gums and patches, are the only ones that are effective in aiding tobacco withdrawal; they reduce the deprivation syndrome, thereby facilitating smoking cessation and increasing its success rate. The stronger the dependence to nicotine the greater their efficacy. The insufficient results obtained at mid-term prove that replacement therapies alleviate only the dependence to nicotine and that the psychological dependence should not be overlooked.

Humans↗
PubMed1993

Effects of the blockade of the renin-angiotensin system in cyclosporin-induced hypertension.

OBJECTIVE: To compare the acute hypotensive effects of three different methods of inhibiting the renin-angiotensin system in a primate model of cyclosporin-induced hypertension. DESIGN: The effects of maximally effective doses of an angiotensin I converting enzyme inhibitor, antihuman renin antibodies or a renin inhibitor (Ro 42-5892) on arterial pressure were evaluated in cyclosporin-treated monkeys. METHODS: Squirrel monkeys were made hypertensive by a 4-week treatment with oral cyclosporin (30 mg/kg) and were equipped with a telemetry system in order to measure arterial blood pressure in the conscious state. RESULTS: Each inhibitor induced a complete suppression of plasma angiotensin II 1 h after administration. The renin antibodies did not decrease blood pressure. Cilazapril decreased blood pressure and Ro 42-5892 was more effective than cilazapril. Moreover, when the renin inhibitor was administered after injection of renin antibodies (rabbit antiserum, 0.4 ml intravenously) or after cilazapril (10 mg/kg orally), it induced a supplementary fall in blood pressure. CONCLUSIONS: These data demonstrate that in this experimental model of hypertension the three different methods of maximal inhibition of the renin-angiotensin system do not lead acutely to the same blood pressure decrease. The results also suggest that renin inhibition might be more effective than angiotensin converting enzyme inhibition in certain forms of hypertension.

Angiotensin I↗
PubMed1993

The vasodilatory effect of endogenous nitric oxide is a major counter-regulatory mechanism in the spontaneously hypertensive rat.

OBJECTIVE: A decreased responsiveness to endothelium-dependent vasodilatory substances is characteristically seen in isolated arteries from spontaneously hypertensive rats (SHR). However, the precise status and role of nitric oxide (NO), which is, at least in part, the endothelium-derived relaxing factor, remains unclear in SHR. The objective of the present study was to evaluate the importance of NO release in vivo. METHODS: The effect on systolic blood pressure of chronic administration of NG-nitro-L-arginine methyl ester (L-NAME, an NO-synthase inhibitor) was studied. Twenty SHR and 10 Wistar-Kyoto (WKY) rats were given 25 mg/kg per day L-NAME by gavage. Thirteen SHR and 14 WKY rats given water for the same period were used as controls. Rats were killed after 15 days and the aortic wall cyclic GMP (cGMP, the second messenger of NO) and cGMP-dependent kinase (the effector of cGMP) concentrations were assessed. RESULTS: During the trial, 11 of the 20 SHR given L-NAME died. Mean +/- SD systolic blood pressure increased from 131 +/- 8 to 171 +/- 10 mmHg in WKY rats given L-NAME and from 185 +/- 10 to 249 +/- 22 mmHg in SHR given L-NAME. Aortic cGMP content was similar in control WKY rats (2122 +/- 707 fmol/mg protein) and in control SHR (2098 +/- 704 fmol/mg protein), and was decreased in the L-NAME-treated WKY rats and SHR to 308 +/- 87 and 644 +/- 222 fmol/mg protein, respectively. The aortic concentrations of cGMP-dependent kinase were not different in any group. CONCLUSIONS: Basal release of NO does not appear to be impaired in SHR, but represents a major counter-regulatory mechanism in this genetic model of arterial hypertension.

Animals↗
PubMed1993

Effects of Ro 40-5967, a new calcium antagonist, and enalapril on cardiac remodeling in renal hypertensive rats.

The goal of the present study was to compare the effects of an angiotensin-converting enzyme (ACE) inhibitor (enalapril) and a long-acting calcium antagonist (Ro 40-5967) on cardiac remodeling secondary to renovascular hypertension. For this purpose, two kidney-one clip (2K-1C) hypertensive rats, 6 weeks after renal artery clipping, were either untreated or treated for 5 weeks with equihypotensive doses of enalapril (3 mg/kg/day) and Ro 40-5967 (30 mg/kg/day). At the end of the treatment period, cardiac weight, maximum coronary blood flow ([MCBF], measured in isolated perfused hearts), and interstitial and perivascular collagen volume fraction (measured by morphometry) were evaluated in all rats. Both drugs similarly decreased arterial blood pressure (ABP) for 24 h. Enalapril was more effective than Ro 40-5967 in inducing regression of cardiac hypertrophy. MCBF was decreased in untreated hypertensive rats and was increased to the same extent by both treatments, although not normalized. Interstitial cardiac collagen content after 11 weeks of hypertension was not increased in untreated hypertensive rats. In contrast, the collagen volume fraction measured in the perivascular area was increased in untreated hypertensive rats and this increase was not significantly suppressed by either enalapril or Ro 40-5967. These results show that cardiac hypertrophy, decrease in MCBF and increase in myocardial collagen content, do not evolve in parallel in 2K-1C hypertensive rats. Two antihypertensive treatments, enalapril and Ro 40-5967, increased MCBF to the same extent but had different effects on cardiac hypertrophy despite having equal antihypertensive efficacy.

Animals↗
PubMed1993

Continuous versus intermittent angiotensin converting enzyme inhibition in renal hypertensive rats.

Converting enzyme inhibitors impair renal function of the kidney beyond a stenosis of the renal artery in humans and induce histological lesions in the clipped kidney of renal hypertensive rats. In two-kidney, one clip hypertensive rats, we compared the time course and magnitude of the biochemical effects of angiotensin converting enzyme inhibition on the plasma renin-angiotensin system, cardiac hypertrophy, renal lesions, and 24-hour blood pressure decrease induced by either intermittent angiotensin converting enzyme inhibition administration (benazepril PO, 10 mg/kg once a day, n = 93) or continuous administration (benazeprilat, 3 mg/kg per day via osmotic pumps, n = 92). Control rats (n = 91) received the drug vehicle intermittently or continuously. Mortality was significantly reduced by both intermittent (n = 3/93) and continuous (n = 3/92) inhibition compared with controls (n = 18/91) (P < .001). Changes in the plasma renin-angiotensin system and blood pressure were parallel. A continuous suppression of the activity of the plasma renin-angiotensin system was associated with a 24-hour decrease in blood pressure with continuous inhibition, whereas intermittent inhibition induced a similar fall in blood pressure only for the first hours after gavage.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin II↗
PubMed1993

Cardiac weight in hypertension induced by nitric oxide synthase blockade.

Wistar rats given a nitric oxide synthase inhibitor, NG-nitro-L-arginine-methyl ester (L-NAME), for 4 weeks develop time- and dose-dependent hypertension without cardiac hypertrophy. This initial study of the relation between left ventricular weight and L-NAME-induced hypertension has now been extended by giving 50 mg/kg per day L-NAME to Wistar rats (n = 30) for 8 weeks and comparing results with those from control rats (n = 10) and two-kidney, one clip rats (n = 14). Although L-NAME rats and two-kidney, one clip rats had increased systolic blood pressures during the last 3 weeks of the experiment (202 +/- 24 and 224 +/- 16 mm Hg, respectively), the ratio of left ventricular weight to body weight of L-NAME rats (2.12 +/- 0.32 mg/g) was not statistically different from that of control rats (1.93 +/- 0.13 mg/g), whereas that of two-kidney, one clip rats was increased (2.85 +/- 0.20 mg/g). The plasma renin activity of L-NAME rats was not significantly different from that of control rats. Two L-NAME rat subgroups were defined according to the presence of left ventricular hypertrophy (ratio of left ventricular weight to body weight > 2.19 mg/g, control mean +2 SD) (6 of 25) or its absence (19 of 25). Systolic blood pressure, plasma renin activity, and cardiac angiotensin converting enzyme activity of L-NAME rats with left ventricular hypertrophy were significantly higher than those of the subgroup without.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensins↗
PubMed1993

Self blood pressure measurement at home.

Forty-six untreated patients measured their blood pressure at home for three weeks using an A and D, UA 751 automatic device, and were examined three times at the outpatient clinic. Home blood pressure was significantly lower than clinic blood pressure, even at the third visit when the correlations between clinic and home values were the most significant. The differences between clinic and home values had a gaussian distribution. The variance analysis of home blood pressure values showed that 67% of the variance was attributable to the between-subject component, 2% to the day effect, 15% to the time of the day effect and 16% to the residual (the measurement error). The standard deviation of the difference between two five-day periods of self blood pressure monitoring at home (5.4 and 4.1 mm Hg) was much lower than what has been reported for clinic measurements or 24-hour ambulatory monitoring.

Adult↗
PubMed1993

[Vasodilator effect of nitric oxide is a necessary counter-regulation in the spontaneously hypertensive rat].

The chronic inhibition of NO-synthase by NG-nitro-L-arginine methyl ester (L-NAME, a L-arginine analogue) induces a dose-dependent decrease in aortic cGMP and an increase in blood pressure. We used this pharmacological approach to evaluate the release of NO in vivo in spontaneously hypertensive rats (SHR); 15 SHR and 10 Wistar-Kyoto rats (WKY) were given 25 mg L-NAME/kg/d by gavage for 15 days; 10 SHR and 10 WKY rats given water for the same period were used as control. During the trial, 10/15 SHR given L-NAME died. Systolic blood pressure (mmHg) increased from 132 +/- 6 to 170 +/- 4 in WKY given L-NAME and from 169 +/- 4 to 242 +/- 6 in SHR given L-NAME. Aortic cGMP content (fmol/mg protein) was 2,204 +/- 382 and 2,076 +/- 461 fmol/mg control WKY and SHR (NS), and was decreased to 324 +/- 44 and 641 +/- 70 in WKY and SHR given L-NAME respectively (p < 0.0001 each). L-NAME increased plasma atrial natriuretic factor only in SHR. In summary, basal aortic cGMP content, reflecting the basal release of NO, was similar in WKY and SHR. The decrease in aortic cGMP content of SHR given L-NAME, due to the blockade of NO-synthase, was accompanied by a large increase in systolic blood pressure and a tremendous mortality rate. Thus, basal release of NO is probably not impaired in SHR, but represents a major counterregulatory mechanism in this genetic model of arterial hypertension.

Amino Acid Oxidoreductases↗
PubMed1993

Critical assessment of international clinical development programmes for new antihypertensive drugs.

Criteria for assessing new antihypertensive drugs: The major factors to be assessed when registering a new antihypertensive drug are chemical quality, drug efficacy, safety and tolerability in the short and long term. Critical criteria for acceptance of the drug may include the degree of originality, the validity of the dose range and administration schedule and the degree of usefulness compared with other drugs used in the same patient group. Future clincial development: The clinical development of new antihypertensive drugs is becoming increasingly complex. Similar errors are repeated from one clinical development programme to another. Simple but original protocols, using average rather than closely selected patient sets, and clearcut dose-ranging studies will reflect a better use of human and financial resources.

Antihypertensive Agents↗
PubMed1993

Critical assessment of combination therapy development.

Although antihypertensive treatment has been found to reduce cardiovascular morbidity and mortality, hypertensive patients are still at a significantly increased risk compared with normotensive controls. One of the reasons is that blood pressure control is often suboptimal. In fact, less than 40% of patients reach the target set by the treating physician. The development of wisely chosen fixed combinations could be one means, among others, to improve blood pressure control without compromising tolerability. The prescription, in a single pill, of two antihypertensive agents has the potential advantage of improving compliance by reducing the number of pills that need to be taken per day. There should be a pharmacological rationale, with the two agents having different and complementary modes of actions to reduce blood pressure: for example, a vascular selective calcium antagonist lowers total peripheral resistance and a beta-blocker lowers heart rate and, thus, cardiac output. These drugs can also mutually neutralise some of each others' side-effects, such as the initial heart rate increases which may occur with dihydropyridine calcium antagonists, and the rise in peripheral resistance elicited by some beta-blockers. The creation of a fixed-dose combination for effective and safe treatment of hypertension requires a complex programme of development. An example is the formulation of a combination tablet of felodipine and metoprolol in which extended-release techniques were applied to ensure that blood pressure control was maintained throughout the 24-h dosing interval. Evaluation included pharmacokinetic studies of the formulation, interaction studies and clinical trials of crossover and parallel-group designs to establish the 24-h efficacy and safety of the product.(ABSTRACT TRUNCATED AT 250 WORDS)

Antihypertensive Agents↗
PubMed1993

Anthology of the renin-angiotensin system: a one hundred reference approach to angiotensin II antagonists.

AIM: To provide a historical overview of the renin-angiotensin system as a guide to the introduction of a new therapeutic pathway, non-peptide inhibition of a angiotensin II. METHOD: One hundred references were selected as a personal preference, for their originality or for their potential impact on medicine. CONCLUSIONS: This review raises the following questions for future research. (1) Will the long-term cardiovascular effects of angiotensin converting enzyme (ACE) inhibition, angiotensin II antagonism and renin inhibition be similar or not, and dependent or independent of blood pressure levels? (2) What are the local-regional interactions between vasoconstrictor and vasodilator systems, and does the renin-angiotensin system synchronize these regional hemodynamic regulatory mechanisms? (3) If hypertension is the result of an interaction between genetic and environmental factors, do proteins secreted through constitutive pathways contribute to the genetic abnormality (prorenin, angiotensinogen, ACE) while regulated secretion (renin) and other regulatory mechanisms (angiotensin II receptors) provide biological support for the environmental effects?

Angiotensin II↗
PubMed1993

Acute effects of a pseudo-tetrapeptide as renin inhibitor on blood pressure and renin-angiotensin system of sodium-repleted and sodium-depleted hypertensive patients.

The blood pressure and renin-angiotensin system effects of the new renin inhibitor, SR 43845 ([N-(pyridyl-3-propionyl)-phenylalanyl- histidyl-(3S,4S) ACHPA-isoleucylamino]-2-methyl-2-dihydroxy-1,3-propane), were studied in 12 hypertensive patients on a normal sodium intake who received a 30-min infusion of intravenous SR 43845 at one of 3 doses: 30, 100 or 300 micrograms/kg (4 patients per group). Eight further patients were infused with the 300 micrograms/kg dose 24 h after 80 mg furosemide orally. In sodium-repleted patients, the 30, 100 and 300 micrograms/kg doses induced a rapid fall in diastolic blood pressure (DBP) which culminated at 4.5, 7.5 and 3.9 mmHg, respectively. Salt depletion increased the renin inhibitor-induced fall in DBP to 10.8 mmHg. DBP was back to baseline at 60 min after starting the lowest dose and 180 min after starting the highest dose. Heart rate did not change. In four of the sodium-depleted patients, 50 mg captopril was given orally at T = 180 min, when blood pressure had returned to baseline. The decrease in BP (8.8 mmHg) was similar to that initially obtained with the renin inhibitor (10.1 mmHg). Plasma angiotensin (Ang) I was dose-dependently reduced by 62, 93 and 92% of baseline values 10 min after the start of the infusion in sodium-repleted patients, and by 90% in sodium-depleted patients; it returned to baseline in both situations between 180 and 360 min. Plasma Ang II levels changed in parallel with those of plasma Ang I.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

[Cooperative study of systolic arterial hypertension in the elderly patient (SHEP). Comments].

SHEP (Systolic Hypertension in the Elderly Program) is a multicenter controlled therapeutic trial which included 4,736 subjects aged 60 years and over, who had isolated systolic hypertension at three consecutive visits at the outpatient clinic. The treatment, based on low doses of diuretic (chlorthalidone 12.5-25 mg daily) combined, when necessary, with a cardioselective beta-blocker (atenolol 25 to 50 mg daily), significantly reduced the incidence of cerebrovascular and coronary events; the relative risk reduction for total mortality was not statistically significant. The beneficial cardiovascular effects were observed in both sexes, and in the 80+ age group. These results show that this particular therapy applied to this form of hypertension decreases the risk of both coronary and cerebral events, as was already suggested by the meta-analysis of the controlled therapeutic trials performed with diuretics, beta-blockers and other older antihypertensive drugs in patients with permanent diastolic hypertension. They also show the limitations of this therapeutic strategy, which controlled only 50 percent of the patients who were, however, highly selected, especially concerning the absence of associated morbid conditions and treatments. The need for, and feasibility of, new controlled therapeutic trials comparing the mortality and morbidity associated with various new antihypertensive therapies must now be discussed.

Adrenergic beta-Antagonists↗
PubMed1992

Decision to treat mild hypertension after assessment by ambulatory monitoring and World Health Organisation recommendations.

OBJECTIVE: To determine if one ambulatory blood pressure recording over 12 hours could detect those patients with mild hypertension who needed treatment according to the World Health Organisation-International Society of Hypertension (ISH) guidelines based on the causal measurement of diastolic blood pressure at successive visits to a clinic. DESIGN: Comparison of decision to treat based on one ambulatory measurement over 12 hours and standard blood pressure measurements over six months in the same patients. SETTING: Outpatient hypertension clinic. SUBJECTS: 130 men and women with diastolic blood pressure of 90-104 mm Hg at second visit to clinic. MAIN OUTCOME MEASURES: Blood pressure measurements over six months. Measurement from ambulatory monitoring. Decision to treat. RESULTS: Of the 130 patients included, 108 were followed up over the six months. Treatment was started according to WHO-ISH criteria in 44 (13 at the third visit, 13 at the fourth, 18 at the fifth). According to the selected criteria for ambulatory blood pressure monitoring 41 patients would have been treated. Both methods agreed that the same 27 patients required treatment and the same 50 did not, but they did not agree in 31 patients. When calculated at the optimal diastolic blood pressure threshold determined by a receiver operating characteristic curve, the sensitivity, specificity, and positive predictive value of ambulatory blood pressure monitoring were 71% (95% confidence interval 57% to 84%), 82% (72% to 92%), and 66% (51% to 81%), respectively. CONCLUSION: If the WHO-ISH criteria are accepted as the standard for deciding to treat patients with mild hypertension the predictive value of one ambulatory blood pressure recording over 12 hours is too low to detect with confidence those patients who need treatment when managed according to these criteria.

Blood Pressure Determination↗
PubMed1992

Investigation of the biochemical effects of renin inhibition in normal volunteers treated by an ACE inhibitor.

1. In order to investigate accurately the biochemical effects of renin inhibition in man, we have developed a sensitive assay to measure angiotensin I (1-10) decapeptide. 2. Angiotensins were extracted from plasma by adsorption to phenylsilylsilica, and angiotensin I (Ang I) was quantified by radioimmunoassay. The detection limit was 0.77 fmol ml-1, and the extraction recovery of [125I]-Ang I added to albumin buffer was 83% at the inflection point (10 fmol ml-1) of the standard curve. The overall recovery was 98.5 +/- 3.5%. The intra- and inter-assay reproducibility was 10.4% and 9.7% respectively. Cross-reactivity of the antiserum used was low (less than 0.3%) with all angiotensin peptides tested except Ang (2-10) nonapeptide. 3. A human pharmacological model was subsequently used to assess in vivo the biochemical effects of the renin inhibitor CGP 38560A. Six healthy volunteers received 20 mg lisinopril, a long-acting ACE-inhibitor. During the following 24 h, the renin-angiotensin system was reset with typically elevated active plasma renin and Ang I, at respectively 275 and 429% of basal values. 4. In a randomized three-way cross-over protocol, the six volunteers received a 30 min infusion of the renin inhibitor CGP 38560A (125 or 250 micrograms kg-1) or 5% glucose. The fall in plasma Ang I was 92% and 97.5% after the lowest and highest dose of the renin inhibitor, respectively. A concomitant increase in active plasma renin was observed.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗