Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.15.1 (ACE)
 18,300 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. Nitric oxide (NO) has been suggested as the mediator of the vascular response to bradykinin. In the present study, we found that NO did not mediate the hypotensive response to bradykinin. In addition, the significance of kininase II in terminating a kinin-induced hypotension and the role of the adrenergic system in compensating for the acute fall in blood pressure (BP) was established. 2. In normal rats, the NO-synthase inhibitor N omega-nitro-L-arginine methyl ester (L-NAME) induced a rise in basal BP (delta BP = 40 +/- 6 mmHg, P < 0.0014) which was not altered by pretreatment with phentolamine (delta BP = 50 +/- 6 mmHg, NS). L-NAME did not attenuate the acute fall in BP in response to bradykinin (3-30 micrograms kg-1) or kallikrein (6-300 micrograms kg-1). However, a significant decrease was observed in the duration of the hypotensive response (P < 0.027). This shorter duration was not observed after pretreatment with phenotolamine in addition to L-NAME. Phentolamine alone prolonged the hypotensive response to bradykinin (P < 0.04). These experiments confirm the role of NO-formation as a hypotensive component in BP homeostasis but not the role of NO as a mediator in kinin-induced hypotension. It further shows that the continuous NO-release also impedes the compensatory adrenergic hypertensive response following the acute fall in BP induced by bradykinin. 3. The hypertensive response to intravenously administered phenylephrine was found to be unchanged by preadministration of L-NAME (NS) thus showing that L-NAME did not change the sensitivity to the adrenergic response. In a separate protocol on L-NAME-treated rats we found no difference in heart rate (NS) during the recovery period following bradykinin before as compared to after administration of phentolamine. It was therefore concluded that the observed alterations in the duration of the hypotensive response were most probably due to changes in peripheral vascular resistance.4. To confirm further that NO is not a mediator in kinin-induced hypotension, we used an experimental model where the response to bradykinin was prolonged by preventing kinin degradation by kininase II-converting enzyme inhibitor (CEI). To produce a hypotensive response purely dependent on kinin, the studies were performed after removal of the renin-angiotensin system by nephrectomy (Nx). In this model, bradykinin (6 microg kg-1, i.v.) induced a prolonged hypotensive response. Pretreatment with LNAME did not alter the magnitude or the progression of the hypotensive response to bradykinin, thus confirming that NO was not a mediator in BK-induced hypotension.5. To study the mechanisms involved in terminating the hypotensive response to bradykinin, the results from the Nx CEI-treated rats were compared with Nx animals not treated with CEL. In the latter group,bradykinin induced a short hypotensive response, i.e. 0.5 +/- 0.1 min as compared to the 17 +/- 1 min after CEI (P<0.003). After kininase II-inhibition (and L-NAME), BP recovery was totally dependent on the adrenergic system, since phentolamine prevented a recovery in BP during the experimental period(P<0.01, compared to the CEI/L-NAME group). These results demonstrate the importance of kininase II as the major agent in terminating a bradykinin-induced hypotension, whereas the adrenergic system plays a small, although significant role in compensating for the fall in BP. The continuous release of NO therefore not only lowers basal BP but also impedes the compensatory adrenergic response.
 ...
PMID:The role of nitric oxide, adrenergic activation and kinin-degradation in blood pressure homeostasis following an acute kinin-induced hypotension. 788 14

One of the greatest challenges of cardiovascular prevention is to minimize the risk of cardiovascular events through the achievement of target lipid levels. Its importance is suggested by the comprehensive meta-analyses of large scale clinical trials and the therapeutic guidelines determining everyday clinical practice. The attainment of target levels is often emphasized, nevertheless, there is a gap between theory and practice. The authors compare the goal attainment rate based on Hungarian medical literature and their own data, and analyze the possibilities of further improvement. The CEL Program evaluated the achievement rate of target total cholesterol levels in more than 10 000 patients of general practitioners in 2004, 2005 and 2006, and the ratio increased from 12% to 30% within 3 years. According to the results of the Hungarian REALITY study the rate of patients achieving the target total cholesterol levels was 21% in 2004, and it increased to 27% during a 3-year period. To this very low improving rate also belongs the fact that in 2007, when only one fourth of patients were on target levels, 87% of general practitioners and 56% of specialists reconciled themselves to it and did not propose any modification in the therapy of patients not achieving the target levels. The surveys conducted at the department of internal medicine with cardiological profile of the county hospital in Gyula proved a considerable increase in the last 7 years in the administration of drugs improving the life expectancy of cardiovascular patients (aspirin, beta-blockers, ACE-inhibitors and statins) due to the widespread application of clinical guidelines and the special attention; nowadays the administration rate is above 90% in all four groups. Nevertheless, the rate of patients achieving the LDL-cholesterol goals was 37% in the high risk and 18% in the very high risk groups in December 2007 and January 2008. The fact that in the latter group only 21% of patients received combination therapy indicates that improving this ratio may be the next step. A greater emphasis should be placed on the achievement of target levels and regular revision of applied medical therapy, particularly in the high and very high risk patients as these groups can benefit the most from it.
 ...
PMID:[A change of attitude in lipidology, achievement of target levels. What comes next?]. 1880 56