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  • hypertension  (2)
  • SMOOTH MUSCLE CONTRACTILITY  (1)
  • 1
    ISSN: 1432-1041
    Keywords: renin-angiotensin system ; chlorthalidone ; hypertension ; multicentre study ; plasma renin activity ; dose prediction
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary It has been established that angiotensin II stimulation may limit the antihypertensive potential of diuretic therapy in some patients. It is less clear, however, whether renin-angiotensin II stimulation is the cause of the flat blood pressure dose-response relationship to diuretics. To investigate this, 75 out-patients with essential hypertension were treated with chlorthalidone 12.5, 25 or 50 mg o.d. for 3 weeks, in a double-blind, placebo controlled cross-over study. Chlorthalidone significantly reduced blood pressure in all the groups, a plateau being reached at 25 mg o.d. Similarly, plasma renin activity was increased by each dose level of chlorthalidone, but it showed a different trend, being increased to a comparable extent at 12.5 mg and 25 mg o.d., and still higher at 50 mg o.d. Thus, greater stimulation of renin was coincident with the levelling of the blood pressure response to chlorthalidone. However no significant correlation was found between interindividual plasma renin activity and change in blood pressure, either in the entire series, or in each treatment subset. The data suggest overall that renin stimulation may influence the characteristic dose-hypotensive response relationship to diuretic agents in antihypertensive therapy, but it is unlikely that measurement of individual plasma renin activity will provide an useful guide to the optimal dose of a diuretic agents.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-1041
    Keywords: calcium antagonists ; nicardipine ; hypertension ; placebo effect ; slow-release preparation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The magnitude and duration of the anti-hypertensive effect of slow-release nicardipine (SR-Nicardipine) have been compared with placebo in 36 uncomplicated essential hypertensives (diastolic BP 95 to 115 mm Hg after 1-month placebo washout). According to a double-blind, randomized, cross-over design they received SR-Nicardipine 40 mg b.d. and placebo for 1 month. At the end of each treatment period, blood pressure and heart rate were measured 12 h after the evening dose and 1, 2, 3 and 4 h after the morning dose. SR-Nicardipine significantly reduced systolic (SBP) and diastolic (DBP) blood pressure at each time after dosing. The absolute decrements peaked 4 h after dosing (−18.3 and −11.7 mm Hg, respectively) and more than 90% of the peak effect persisted 12 h after dosing, both for SBP and DBP. The heart rate was slightly increased by SR-Nicardipine. Adverse effects monitored with a check-list occurred in 31% of patients during SR-Nicardipine treatment and in 28% on placebo. Thus, SR-Nicardipine 40 mg b.d. has a maintained and significant antihypertensive effect lasting up to 12 h in essential hypertension.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1573-2568
    Keywords: EXPERIMENTAL COLITIS ; SUBSTANCE P RECEPTOR ANTAGONIST ; HISTOLOGY ; SMOOTH MUSCLE CONTRACTILITY
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The etiology of inflammation, edema, and smoothmuscle contraction characteristic of inflammatory boweldisease is not clearly understood. There is evidencethat several neuropeptides, including substance P (SP), may play a role. In this study weevaluated the ability of a SP-antagonist (SR140333) tomodify the course of experimental colitis induced in therat by trinitrobenzene sulfonic acid (TNB). Colitis was induced in 24 rats using TNB applied byintrarectal enema. Twelve TNB-treated rats receivedSR140333, 0.1 mg/kg intraperitoneally, 30 min before theadministration of TNB and every 48 hr until death. Twelve rats receiving only intrarectal 0.9%saline served as controls. Rats of each group werekilled after 14 days. At day 14, the control groupshowed no signs of inflammation whereas the TNB-treated rats without SR140333 treatment exhibited awell-established colitis. The TNB-treated group had ahigher level of inflammation, as seen histologically andby the significantly greater weight of colon strips, compared to the controls (0.30 ± 0.09 gvs 0.13 ± 0.03 g, P 〈 0.001) and to theSR140333-treated rats (0.30 ± 0.09 g vs 0.14± 0.05 g, P 〈 0.001). In addition, smoothmuscle contractility was significantly reduced in the inflamedcolons of TNB-treated rats when compared with thecontrols (carbachol: 42.7 ± 20.3 vs 254.2± 69.78 mg/mm2± 10.02 vs 89.45± 23.17 mg/mm2 11.4 ± 2.2 vs 98.32 ± 33.57mg/mm21). However, SR140333-treated ratsshowed a recovery from inflammation and motoralterations caused by TNB (carbachol: 150.9 ±46.1 mg/mm21; SP: 32.5 ± 9.4 mg/mm25; KCl:125.7 ± 36.1 mg/mm21). In conclusion,treatment with SP antagonist SR140333 reduces theseverity of colitis and has beneficial effects on theconcomitant alterations of contractility. Thus, theblockade of substance P may represent a possibility inthe treatment of intestinal inflammation.
    Type of Medium: Electronic Resource
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