Treatment of allergic rhinitis can improve blood pressure control.

Owing to high prevalence of arterial hypertension (AH) and allergic rhinitis (AR), these diseases frequently coexist. The study aimed to assess whether improvement of AR by conventional treatment can improve blood pressure (BP) control in this population. Sixty-eight subjects of both sexes aged 35-60 years with AR and AH were randomized into two groups to receive in addition to their antihypertensive medications: treatment group (n=34) Fluticasone nasal 50 microg/spray b.i.d. and Fenoxifenadine 180 mg tablets q.d., and control group (n=34) 0.9% NaCl nasal drops b.i.d. Office BP and AR severity (using the Relative Quality of Life Questionnaire (RQLQ)) and high-sensitive C-reactive protein (hs-CRP) were measured at study entry and after 8 weeks in both groups, without changing of antihypertensive medications. In Treatment group an improvement in RQLQ, significant reduction of systolic BP (SBP) (DSBP 7.4 +/- 4.3 mm Hg, P=0.006) and reduction of hs-CRP level (DCRP 2.05 +/- 1.08; P=0.028) were observed, whereas diastolic BP (DBP) remained unchanged (DDBP 0.9 +/- 1.7 mm Hg, P=0.7). There was a significant correlation between DRQLQ and DSBP (r=0.86; P=0.019) and between DCRP and DSBP (r=0.56; P=0.027). No statistically significant changes of RQLQ, BP and CRP were observed in the control group. In patients with coincidence of AH and AR, medications meant to improve AR attenuate low-grade systemic inflammation and can lower SBP, but not DBP.

Interactions of angiotensin-converting enzyme, kinins and nitric oxide in circulation and the beneficial effects of ACE inhibitors in cardiovascular diseases.

Renin-angiotensin-aldosterone systems play a critical role in the development and progression of cardiovascular diseases, and inhibitors of angiotensin-converting enzyme have proven effective for the treatment of these diseases. Since angiotensin II receptor antagonists can inhibit the effects of angiotensin II via ACE-independent pathways, e.g., chymase, they were considered to be more effective than ACEIs. On the other hand, ACE inhibitors can increase bradykinin, and thus, nitric oxide, which may cause potent cardioprotection, inhibition of smooth muscle proliferation and attenuation of inflammation mechanisms. It appears that angiotensin II receptor antagonists and ACEIs may mediate cardioprotection in different ways. This is the rationale to explore the possibility of a combined administration of both drugs for the treatment of chronic heart failure and other cardiovascular pathology. In this review we try to analyze the role of ACE, kinins and chymase inhibition in the pathophysiology and treatment of cardiovascular diseases.

The effect of an endothelin-receptor antagonist, bosentan, on blood pressure in patients with essential hypertension. Bosentan Hypertension Investigators.

BACKGROUND: Endothelin is a powerful vasoconstrictor peptide derived from the endothelium. We evaluated the contribution of endothelin to blood-pressure regulation in patients with essential hypertension by studying the effect of an endothelin-receptor antagonist, bosentan. METHODS: We studied 293 patients with mild-to-moderate essential hypertension. After a placebo run-in period of four to six weeks, patients were randomly assigned to receive one of four oral doses of bosentan (100, 500, or 1000 mg once daily or 1000 mg twice daily), placebo, or the angiotensin-converting-enzyme inhibitor enalapril (20 mg once daily) for four weeks. Blood pressure was measured before and after treatment. RESULTS: As compared with placebo, bosentan resulted in a significant reduction in diastolic pressure with a daily dose of 500 or 2000 mg (an absolute reduction of 5.7 mm Hg at each dose), which was similar to the reduction with enalapril (5.8 mm Hg). There were no significant changes in heart rate. Bosentan did not result in activation of the sympathetic nervous system (as determined by measurement of the plasma norepinephrine level) or the renin-angiotensin system (as determined by measurements of plasma renin activity and angiotensin II levels). CONCLUSIONS: An endothelin-receptor antagonist, bosentan, significantly lowered blood pressure in patients with essential hypertension, suggesting that endothelin may contribute to elevated blood pressure in such patients. The favorable effect of treatment with bosentan on blood pressure occurred without reflexive neurohormonal activation.

The addition of mibefradil to chronic hydrochlorothiazide therapy in hypertensive patients is associated with a significant antihypertensive effect.

OBJECTIVE: To evaluate the antihypertensive efficacy, tolerability, safety, and dose-response characteristics of the novel calcium antagonist, mibefradil, in combination with a diuretic regimen. DESIGN: A multinational, double-blind, randomised, placebo-controlled, parallel-design trial. METHODS: Three hundred and seven patients whose mild-to-moderate essential hypertension remained uncontrolled after 4 weeks of treatment with hydrochlorothiazide (HCTZ) 25 mg/day and placebo were randomised to receive combined treatment with HCTZ and once-daily doses of 12.5, 25, 50, or 100 mg of mibefradil or placebo. After 8 weeks of combined treatment, HCTZ was withdrawn and the mibefradil groups continued on their respective doses for an additional 6 weeks. RESULTS: After 8 weeks, the addition of once-daily doses of mibefradil to the initial HCTZ regimen resulted in clinically relevant, dose-related reductions in sitting diastolic blood pressure (SDBP) and sitting systolic blood pressure (SSBP) at trough, which were significantly greater in the 50 and 100 mg dose groups compared to the placebo group (P < or = 0.003). Placebo-corrected treatment effects on SDBP and SSBP at the end of the combined treatment period relative to baseline were, respectively, -4.1 and -8.0 mm Hg in the 50 mg mibefradil group and -9.5 and -8.0 mm Hg in the 100 mg mibefradil group. Therapeutic response rates to combination mibefradil and HCTZ therapy were high and dose related, reaching 82% for SDBP in the 100 mg group. CONCLUSIONS: The addition of once-daily doses of 50 or 100 mg of mibefradil to patients whose hypertension is not controlled by HCTZ alone is well tolerated and effective in improving BP control.

A randomised, double-blind trial comparing mibefradil and amlodipine: two long-acting calcium antagonists with similar efficacy but different tolerability profiles. Mibefradil International Study Group.

OBJECTIVE: To compare the efficacy and tolerability of mibefradil and amlodipine in patients with uncomplicated mild-to-moderate essential hypertension. DESIGN: A double-blind, randomised, parallel group multicentre trial. METHODS: 239 patients received 50 mg mibefradil or 5 mg amlodipine for 4 weeks, followed by a forced titration to 100 mg mibefradil or 10 mg amlodipine for an additional 8 weeks. Patients then entered a 4-week withdrawal period either on therapy or switched to placebo. RESULTS: Statistically equivalent reductions in trough sitting diastolic blood pressure (SDBP) were observed after 12 weeks of once-daily treatment with 50/100 mg mibefradil (-11.5 +/- 8.2 mm Hg) and 5/10 mg amlodipine (-13.2 +/- 7.9 mm Hg). The number of patients with normalised SDBP (< or = 90 mm Hg) increased 23.3% in the mibefradil group and 19.5% in the amlodipine group (approximately 74% in both groups). Patients on mibefradil or amlodipine during the withdrawal period had significantly larger decreases in SDBP than those on placebo. Patients on mibefradil had a decrease in heart rate of 5.5 bpm. Patients on amlodipine had no change in heart rate; however, cessation of amlodipine was associated with a decrease in heart rate. CONCLUSIONS: Mibefradil was as effective as amlodipine in reducing BP; both compounds were effective treatments of hypertension.

Time dependency of the antihypertensive efficacy of the new renin inhibitor Ro 42-5892.

The objective of this study was to assess the antihypertensive efficacy of the new renin inhibitor Ro 42-5892 in patients with essential hypertension treated with 100 mg once daily orally. This was a double-blind, placebo-controlled, parallel group trial. After three weeks of wash-out and one week of single-blind placebo run-in periods, 25 patients with mild to moderate essential hypertension (sitting DBP between 95 and 114 mmHg) were randomised to receive either placebo (n = 12) or 100 mg of Ro 42-5892 (n = 13) once daily for eight days. On the eighth day, four hours after the oral administration, patients were randomised to receive intravenously either placebo or 10 mg of Ro 42-5892. BP and heart rate were measured repeatedly (hourly for eight hours and at the 24th hour post-dose) on the first and last days of active treatment. Compared with the placebo group, a slight decrease in sitting DBP was observed after the first dose in the Ro 42-5892 group. The decrease in sitting DBP reached significant levels only at six to eight hours post-dosing. In contrast, on the last day of active treatment, a larger, faster and longer decrease in sitting DBP was observed in the Ro 42-5892 group. Thus, the peak effect (-8.9 +/- 1.9 vs. -2.9 +/- 1.3 mmHg, P < 0.01) was reached 1.5 hours post-dosing and the trough effect (24 hours post-dosing) was slightly but significantly lower when compared with the placebo group (-3.0 +/- 1.0 vs -0.3 +/- 0.8 mmHg, P < 0.05, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of an orally active renin inhibitor, Ro 42-5892, in patients with essential hypertension.

Ro 42-5892 (Ro) is a new renin inhibitor that has been shown to be an orally effective compound in primates and in the first exploratory studies in humans. However, no firm conclusions could be drawn from the human trials and therefore the present study was designed to evaluate the antihypertensive efficacy of the compound in a double-blind, placebo-controlled trial. After a 3 week wash-out period and a 1 week single-blind placebo period, 24 patients were randomized to receive once daily orally either placebo or 600 mg Ro 42-5892 (N = 12/group) for 8 days. On the last day of treatment, an intravenous infusion of placebo or 100 mg Ro was given in a double-blind fashion, 4 h after the oral administration. Blood pressure (BP), heart rate (HR), plasma renin activity (PRA), immunoreactive renin (IRR), and plasma Ro levels were measured repeatedly on the first and last days of treatment. After the first oral intake of Ro, sitting diastolic BP dropped significantly from 30 min to 24 h post-dose when compared to placebo (-10.2 +/- 1.2 mm Hg v - 0.4 +/- 2.0 mm Hg at peak and -6.9 +/- 1.8 mm Hg v 1.7 +/- 0.9 mm Hg at trough; P < .01 respectively). The trough effects of Ro and placebo after the 7th and 8th doses were -5.1 +/- 1.6 mm Hg v -0.2 +/- 1.0 mm Hg; P < .05 and -5.4 +/- 1.3 mm Hg v 2.3 +/- 1.2 mm Hg; P < .01, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Resource savings from non-pharmacological control of hypertension.

Treatment of acute cardiovascular illness is expensive, and a preventative approach may be cheaper. Since pharmacological costs account for a large proportion of costs in prevention programmes, a non-pharmacological approach such as that used by us in Ashkelon on mild hypertensives, relying on stress management, weight management and exercise aimed at reducing risk factors, might prove to be more cost-effective. After six months on a 1,000 calorie/day diet, 69 obese subjects (initial body mass index greater than 28 kg/m2) had reduced their weight by an average of 7.3 kg (P less than 0.005). This weight reduction contributed to a significant decrease in systolic blood pressure (SBP) from 157.3 to 137.6 mmHg (P less than 0.005) and diastolic blood pressure (DBP) from 101.1 to 85.2 mmHg (P less than 0.005), which was sustained at two-year follow-up. Pharmacological treatment could be stopped in about one-quarter of these cases. In non-obese mild-hypertensives, deep muscle relaxation and biofeedback techniques were prescribed. Significant decreases in SBP (153.1 to 138.3 mmHg, P less than 0.005) and DBP (101.2 to 90.1 mmHg, P less than 0.005) were achieved at six months. In nine out of 19 cases pharmacological treatment was stopped after six to eight months. Smoking cessation was achieved by individual instruction together with stress management techniques, physical exercise and a nicotine-based chewing gum. After six months 18 out of 30 heavy smokers had stopped smoking, and the remaining 12 had reduced their cigarette consumption.(ABSTRACT TRUNCATED AT 250 WORDS)

The antihypertensive effect of atenolol and bopindolol in the elderly.

The antihypertensive efficacy and tolerability of two betablockers: atenolol and bopindolol, was compared in a group of 30 elderly subjects aged 64.8 +/- 4.6 years. The daily dose of the two agents was relatively low. Atenolol 50-100 mg and bopindolol 0.5-1.0 mg sufficed to cause reduction of DBP to the target of less than or equal to 95 mm Hg, when applied as monotherapy. This was achieved in 75% of cases with bopindolol and in 93% of cases with atenolol. Atenolol, 50-100 mg/dd, lowered blood pressure from 173.7 +/- 13.2/103.7 +/- 3.0 (weekly) to 155.5 +/- 16.5/86.5 +/- 8.2 mm Hg (week 12) (P less than 0.005) while bopindolol, 0.5-1.0 mg, lowered blood pressure from 171.6 +/- 11.3/104.1 +/- 3.6 to 158.7 +/- 20.9/86.1 +/- 6.0 mm Hg (P less than 0.005). Heart rate was reduced from 80.5 (week 4) to 66.7 +/- 7.3 (week 12) by atenolol (P less than 0.0001), and from 83.7 +/- 11.8 (week 4) to 71.1 +/- 7.5 (week 12) by bopindolol (P less than 0.0001). Between treatment differences: comparisons yielded P values which were not sufficiently low to reject the null hypothesis of no difference between the two treatments. Well-being and short-term memory were not affected by either agent and tolerability of both drugs was good. These findings demonstrate that both bopindolol and atenolol are useful agents for control of hypertension in the elderly.

Is common variable hypogammaglobulinemia linked to HLA? A family study.

Two patients with common variable hypogammaglobulinemia (CVH) and their families, who came from different ethnic backgrounds, were surveyed for the level of immunoglobulins (Ig) and HLA genotypes. Six of 10 siblings and the mother in one family had a decreased level of one of the major classes of Ig (IgA in 5, IgM in 1 and IgG in the mother). A similar decrease was found in three of six siblings in the other family (IgG in one, IgA in one and IgM in one). HLA genotyping disclosed that affected and nonaffected family members had identical genotypes, suggesting that hypogammaglobulinemia in CVH is not linked to a specific HLA genotype.

Norwegian-type scabies mimicking contact dermatitis in an immunosuppressed patient.

Patients taking immunosuppressive drugs are susceptible to various forms of infection, including dermatologic disease. Recently, atypical manifestations of scabies have been reported in such patients. In the case reported here, a 26-year-old woman who had had a renal transplant and was taking immunosuppressive drugs had a pruritic rash on the back that closely resembled contact dermatitis. However, skin scrapings from the involved areas and punch biopsy specimen of the back showed live scabies mites. The pruritus was relieved and the skin lesions disappeared within ten days of treatment with scabicides. We believe that current widespread use of immunosuppressive agents may result in more cases of atypical forms of scabies. Therefore, physicians who deal with immunosuppressed patients should be aware of this possibility.

Familial combined hyperlipidemia and otosclerosis--the occurrence in a large kindred.

The occurrence of otosclerosis and hyperlipidemia in four generations of a single family is described. The lipid abnormality fulfilled the characteristics of combined familial hyperlipidemia. Whereas a genetic linkage between combined hyperlipidemia and otosclerosis is feasible, our study indicates that both conditions are inherited through autosomal but unlinked genes.

A case of familial Mediterranean fever with cutaneous vasculitis and immune complex nephritis: light, electron, and immunofluorescent study of renal biopsy.

A 29-year-old patient suffering from familial Mediterranean fever developed severe myalgia and hematuria. Skin biopsy showed vasculitis. The kidney biopsy revealed diffuse proliferative and exudative glomerulonephritis. On immunofluorescent examination, IgM deposits accompanied by C3 were found in coarse granular peripheral distribution. Electron microscopy revealed glomerular subepithelial deposits. Familial Mediterranean fever with vasculitis and immune complex nephritis is discussed.

Mechanisms of hypertension during the acute and intermediate phases of the one-clip, two-kidney model in the dog.

The acute and intermediate onset phases of one-clip, two-kidney hypertension were studied in six conscious dogs. Mean arterial pressure (MAP), cardiac output (CO), total peripheral resistance (TPR), serum renin concentration (SRC), plasma aldosterone (PA) and cumulative sodium and water balance were studied prior to unilateral renal artery constriction, at 2, 10, and 24 hours postconstriction, and daily thereafter for 5 days. At 2 hours postconstriction, MAP, CO, TPR, and SRC were elevated, with unchanged fluid balance. At 10 and 24 hours there was a further rise in CO accompanied by positive fluid-sodium balance, with a slight decrease in MAP, TRP, and SRC. During days 2 and 3, MAP, CO, TPR, and SRC remained elevated and stable in the presence of decreasing fluid-sodium balance to preconstriction levels. During days 4 and 5, MAP, SRC, and fluid-sodium balance remained unchanged, TPR demonstrated a secondary increase, whereas CO decreased to preconstriction values. Sequential changes in PA parallel those of SRC, but were significant only at 2 hours postconstriction. These changes suggest that the increased CO is not totally dependent on fluid-sodium balance, and that CO is not the sole determinant of elevated MAP. The temporal relationship between MAP and SRC throughout the study is consistent with renin-mediated hypertension. The secondary rise of TPR may be due to total body autoregulation and/or increased vascular reactivity to high levels of circulating angiotensin. A unitary renin-angiotensin mechanism, therefore, may be responsible for the induction and maintenance of hypertension in this experimental model.

Renin stimulation by isoproterenol and theophylline in the isolated perfused kidney.

The intrarenal mechanisms of renin release were studied in the isolated perfused rabbit kidney during stimulation by isoproterenol, 0.01 mug/kg per min, and by theophylline, 0.87 mg/kg per min. In the absence of urinary flow during the early stages of perfusion, isoproterenol caused a 17% increase of renal vein serum renin concentration (RVSRC) (P less than 0.001) without changing renal blood flow, renal vascular resistance, or serum potassium. dl-Propranolol, 2.0 mg/kg per min. abolished this isoproterenol-induced renin release. A moderate reduction in perfusion pressure prior to the infusion of isoproterenol resulted in a marked additional stimulation of renin release. Studies during and following ureteral occlusion demonstrated that theophylline stimulates renin release by decreasing renal vascular resistance, whereas the concomitant increase in sodium transport to the macula densa exerted an opposite effect. dl-Propranolol did not affect theophylline-induced renin secretion. It is concluded that single exogenous stimuli may activate more than one intrarenal mechanism simultaneously. Isoproterenol has a direct renin-stimulatory effect on intrarenal beta-adrenergic receptors that may be reinforced by baroreceptor stimulation. Theophylline stimulates renin via a baroreceptor mechanism, with simultaneous renin suppression via a sodium-macula densa effect.