Inflammatory reactions are believed to be important in nonspecific bronchial hyperreactivity (BHR). To investigate the potential role for oxidant-mediated modulation of BHR, we investigated oxidative metabolism of polymorphonuclear leukocytes (PMN) from the peripheral blood in 28 nonallergic patients with chronic air-flow obstruction (CAO). No difference in O2- was found between 14 smokers and 14 ex-smokers with CAO. A significant correlation was found between the degree of BHR and O2(-)-generation of PMN after stimulation with 20 ng/ml phorbol myristate acetate, both in smokers (r = 0.59, p less than 0.01) and in ex-smokers (r = 0.79, p less than 0.01). In the light of other findings in experimental animal studies, the results suggest a direct or indirect role for O2- in the modulation of BHR. Thus, in nonallergic patients with CAO, BHR and inflammation may be linked in a similar way as in allergic patients with asthma.

ACE inhibitors effectively reduce systemic vascular resistance in patients with hypertension, heart failure or chronic renal disease. This antihypertensive efficacy probably accounts for an important part of their long term renoprotective effects in patients with diabetic and non-diabetic renal disease. The renal mechanisms underlying the renal adverse effects of ACE inhibitors--intrarenal efferent vasodilation with a consequent fall in filtration pressure--are held to be involved in their renoprotective effects as well. The fall in filtration pressure presumably contributes to the antiproteinuric effect as well as to long term renoprotection. The former is suggested by the positive correlation between the fall in filtration fraction and the reduction in proteinuria found during ACE inhibition. The latter is suggested by the correlation between the (slight) reduction in glomerular filtration rate at onset of therapy and a more favourable course of renal function in the long term. Such a fall in filtration rate at the onset of ACE inhibitor treatment is reversible after withdrawal, and can be considered the trade-off for long term renal protection in patients with diabetic and nondiabetic chronic renal disease. In conditions in which glomerular filtration is critically dependent on angiotensin II-mediated efferent vascular tone (such as a post-stenotic kidney, or patients with heart failure and severe depletion of circulating volume), ACE inhibition can induce acute renal failure, which is reversible after withdrawal of the drug. Systemic and renal haemodynamic effects of ACE inhibition, both beneficial and adverse, are potentiated by sodium depletion. Consequently, sodium repletion contributes to the restoration of renal function in patients with ACE inhibitor-induced acute renal failure. Our the other hand, co-treatment with diuretics and sodium restriction can improve therapeutic efficacy in patients in whom the therapeutic response of blood pressure or proteinuria is insufficient. Patients at the greatest risk for renal adverse effects (those with heart failure, diabetes mellitus and/or chronic renal failure) also can expect the greatest benefit. Therefore, ACE inhibitors should not be withheld in these patients, but dosages should be carefully titrated, with monitoring of renal function and serum potassium levels.

Inflammatory reactions are believed to be important in nonspecific bronchial hyperreactivity (BHR). To investigate the potential role for oxidant-mediated modulation of BHR, we investigated oxidative metabolism of polymorphonuclear leukocytes (PMN) from the peripheral blood in 28 nonallergic patients with chronic airflow obstruction (CAO). No difference in O2- generation was found between 14 smokers and 14 ex-smokers with CAO. A significant correlation was found between the degree of BHR and O2- generation of PMN after stimulation with 20 ng/ml phorbol myristate acetate, both in smokers (r = 0.59, p less than 0.01) and in ex-smokers (r = 0.79, p less than 0.01). The results suggest that oxygen radicals in a direct or indirect way may modulate BHR. Thus, in nonallergic patients with CAO, BHR and inflammation may be linked in a similar way as in allergic patients with asthma.

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