Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0085580 (essential hypertension)
 14,686 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Despite the availability and application of more effective antihypertensive drugs over the past 3 decades, hypertension continues to be a major risk factor for the development of premature cardiovascular disease. Moreover, failure to elucidate the pathogenesis of essential hypertension, noncompliance, and difficulties in defining the appropriate level of blood pressure elevation requiring therapy, continue to mitigate against the adequate control of hypertension. Some of these problems may be overcome by the availability of depot forms of antihypertensive medication or implantable drug delivery systems, or by the use of several recently developed antihypertensive drugs. These include dopaminergic agonists, selective alpha-adrenergic agents, calcium antagonists, medullary neutral lipids, gamma-aminobutyric acid agonists, and inhibitors of renin or phenethylamine N-methyl-transferase. In addition, the potential involvement of morphinomimetic peptides, prostaglandins, tonin, and bradykinin in blood pressure control or certain hypertensive states suggests that drugs developed to block or potentiate the actions of these substances may have important therapeutic applications.
 ...
PMID:Speculative approaches in hypertension: concepts and drugs of the future. 626 17

Angiotensin converting enzyme plays a key role in the hormonal regulation of blood pressure. It is responsible for the production of the vasoconstrictor hormonal peptide angiotensin II as well as the destruction of the vasodilator peptide bradykinin. Recently, orally active specific inhibitors of angiotensin converting enzyme have become available. Captopril (SQ14225) blocks angiotensin I and potentiates bradykinin effects in vitro and in vivo. In man it leads to a fall in endogenous plasma angiotensin II, a rise in blood angiotensin I and renin, but no change in blood bradykinin can be detected. In sodium deplete normal subjects it lowers the blood pressure, but in sodium replete subjects it is without effect. Similarly, it will acutely lower blood pressure in renovascular and accelerated hypertension but not in essential hypertension. The acute hypotensive effect of captopril may therefore be due to inhibition of the renin-angiotensin system. However, in the long term, it is effective in lowering the blood pressure in patients with essential hypertension, especially when combined with a diuretic. This suggests that the long-term hypotensive effect differs from the short term effect, and involves mechanisms other than inhibition of the renin-angiotensin system. This may include local effects on blood vessels and the kidney and the kallikrein-kinin system.
 ...
PMID:Vasoactive peptides and hypertension: role of angiotensin converting enzyme. 626 79

The recent development of several inhibitors of the renin-angiotensin system has perfected our knowledge of the part played by this system in the control of physiological and pathological arterial pressure. Peptides inhibiting angiotensin II, such as Sar1, Ala8 angiotensin II, block the peripheral effects of angiotensin on vascular renal and adrenal receptors. Inhibition of the conversion enzyme, notably with captopril, prevents the formation of angiotensin II from angiotensin I and also results in accumulation of a vasodilator and natriuretic peptide: bradykinin. Finally, it is now possible to inhibit more specifically the reaction of renin with its substrate, angiotensinogen, by using pepstatin or its derivatives, or peptide analogues of the substrate. The use of these inhibitors, especially captopril (so far the most studied), has made it clear that renin plays a part in experimental and human essential hypertension and participates in the control of arterial blood pressure in subjects with normal sodium intake.
 ...
PMID:[The renin-angiotensin system and its inhibition (author's transl)]. 626 54

1. The acute hormonal and hypotensive effects of MK 421 (10 mg p.o.) were assessed by a double-blind randomized trial in twelve subjects with essential hypertension. The study was performed during a normal and low salt intake. 2. Plasma angiotensin converting enzyme (ACE) activity was maximally inhibited by 57 (s.e.m. = 4)% of control activity at 4-8 h. Plasma ACE was still depressed at 24 h by 10% of control activity but had returned to normal by 32 h. 3. Sodium depletion did not alter basal plasma ACE activity, nor change the degree of inhibition of MK 421. 4. Plasma angiotensin II was depressed during ACE inhibition, but no change in circulating bradykinin was detected. Reciprocal rises occurred in plasma renin and angiotensin I levels with a time course similar to ACE inhibition. 5. All subjects showed a fall in their blood pressure, maximal between 6-8 h. Mean arterial pressure fell 12 (s.e.m. = 5) mmHg on the normal sale intake and 16 (s.e.m. = 3) mmHg on the low salt diet, at 8 h. 6. Blood pressure and angiotensin converting enzyme activity changes were significantly correlated (r = 0.86, n = 12).
 ...
PMID:Correlation between angiotensin converting enzyme inhibition and the acute hypotensive response to MK 421 in essential hypertension. 629 32

In order to investigate the possible role of bradykinin in the hypotensive mechanism of angiotensin I converting enzyme inhibitor (Captopril) in renin-independent essential hypertension (EHT), we studied the effects of the single administration of 100 mg captopril on plasma bradykinin levels by sensitive radioimmunoassay in 21 EHT, who showed agonistic responses to 1Sar, 8Ile-angiotensin II (A IIA). Fourteen of the patients were low renin and 7 were normal renin EHT. There was no correlation between the baseline plasma renin activity (PRA) and the fall in mean blood pressure (MBP) following captopril administration. When the patients were analyzed according to MBP response, the responders (R) showed a significantly greater bradykinin increment (delta BK, +64%) (p less than 0.05), whereas the nonresponders (NR) did not show such an increase. There was a positive correlation between delta BK and the MBP reduction after captopril in the R group (r = 0.623, p less than 0.05). Plasma aldosterone (PA) decreased profoundly in the R group (-36% from baseline, p less than 0.05). Pretreatment ACE activity was significantly higher in the R group than in the NR group (p less than 0.05). Pressor response to A IIA showed a significantly (p less than 0.05) greater response after captopril administration in the R group. There were no significant differences in blood concentration of captopril between the R and NR groups. The present results suggest that bradykinin may be involved in the hypotensive action of captopril in the EHT subgroup, where the renin-angiotensin system appears to play an inert role for the elevation of blood pressure.
 ...
PMID:[Antihypertensive mechanism of oral angiotensin I converting enzyme inhibitor (captopril) in renin-independent essential hypertension]. 631 35

Bradykinin (BK) and [des-Arg9]-bradykinin (-9BK) concentrations in blood and urine samples from 18 normotensive subjects and 23 patients with low-renin essential hypertension were determined by radioimmunoassay. BK and -9BK levels in venous blood from normotensive subjects were 67.1 +/- 60.8 pg/ml and 204.1 +/- 44.5 (mean +/- S.D.), respectively, and levels in urine from normotensive subjects were 5.3 +/- 5.3 ng/ml and 1.6 +/- 1.2, respectively. The blood and urinary levels of BK and -9BK in low-renin essential hypertensives were not significantly different from those of normotensives and did not change when the hypertensives were treated with the new orally active angiotensin I-converting enzyme (ACE) inhibitor, enalapril (MK421). It has been proposed that BK levels do not change with ACE inhibition because under these conditions BK might be metabolized to -9BK by kininase I. Since -9BK levels did not increase with MK421 treatment, this possibility can be excluded. The absence of elevations in blood and urine BK and -9BK after administration of MK421 does not support an involvement of kinins in the mechanism of antihypertensive action of MK421 in these patients. On the basis of the data, it is not possible to exclude such an involvement, however, because local changes in kinin concentrations could occur that are not reflected by changes in circulating or urinary kinin levels.
 ...
PMID:Immunoreactive bradykinin and [des-Arg9]-bradykinin in low-renin essential hypertension--before and after treatment with enalapril (MK 421). 631 33

Angiotensin-converting enzyme, or kininase II, is a zinc metallo-enzyme; the cation forms part of its active site. The enzyme transforms angiotensin I into angiotensin II and hydrolyses bradykinin into inactive peptides. Antihypertensive diuretics may decrease the activity of the angiotensin-converting enzyme by increasing urinary zinc excretion. Captopril inhibits the angiotensin-converting enzyme, but also affects electrolyte excretion and should be reassessed as a possible first-choice antihypertensive agent in the treatment of essential hypertension.
 ...
PMID:Zinc, angiotensin I-converting enzyme and hypertension. 631 70

The renin-angiotensin system is the most important hormonal system in the control of blood pressure. It can be blocked at several steps in its reaction pathway. Angiotensin-converting enzyme, or kininase II, is responsible for catalysing the formation of vasoconstrictor angiotensin II as well as for the breakdown of the vasodilator bradykinin. With the advent of specific orally active angiotensin-converting enzyme inhibitors (captopril and enalapril) a practical and effective means of blocking angiotensin formation is now clinically available. ACE inhibitors are effective long-term therapy in patients with essential hypertension. They are particularly useful in the treatment of severe accelerated drug-resistant hypertension and renovascular hypertension, and the agents of choice for afterload reduction in severe congestive cardiac failure. They have several pharmacological advantages, important in anaesthetic practice, over other hypotensive agents. They have no central nervous or autonomic nervous system effects. Thus, patients being treated with ACE inhibitors retain normal sympathetic cardiovascular responses.
 ...
PMID:Pharmacology of agents acting on the renin-angiotensin system. 631 3

In order to clarify the role of the kallikrein-kinin system in the hypotensive mechanisms of converting-enzyme inhibition, captopril was administered in a single oral dose of 50 mg to 17 hypertensive patients, of whom 14 had essential hypertension, one had chronic renal failure, one had primary aldosteronism, and one had glucocorticoid responsive hyperaldosteronism. Captopril lowered blood pressure remarkably in either low-renin or normal-, and high-renin hypertensives, however, there was no significant relationship between the fall in blood pressure and pretreatment levels of plasma renin activity (PRA) in any of the patients any time after the administration. PRA was significantly increased in normal- and high-renin hypertensives but not in low-renin patients. Plasma aldosterone concentration (PAC) was decreased significantly in normal- and high-renin patients, while no significant change in PAC was observed in patients with low-renin activity. Captopril elevated plasma bradykinin concentration (PBK) from a control value of 12.5 +/- 4.1 (mean +/- s.d.) to 20.3 +/- 7.7 pg/ml (p less than 0.001) at 30 min, and there was a significant correlation between changes in PBK and changes in mean blood pressure 120 min after the administration in all the patients (r = 0.741, p less than 0.01, n = 17). In one patient with primary aldosteronism, PBK increased from a baseline of 10.0 to a maximum value of 19.0 pg/ml, corresponding to the rapid fall in blood pressure. Also, in one patient with glucocorticoid responsive hyperaldosteronism, captopril increased PBK from a control of 14.1 to 27.9 pg/ml at 30 min, corresponding to the marked fall in blood pressure from 170/106 to 136/90 mmHg. From these findings, it is suggested that the accumulation of kinins following captopril administration plays a major role in the short-term reduction of blood pressure in hypertensive patients, especially in those with low renin-angiotensin activity.
 ...
PMID:[Acute antihypertensive effect of captopril in hypertensive patients: with special reference to kallikrein-kinin system]. 636 44

The present study was undertaken to quantify the circulating kinins in patients with various cardiovascular diseases using a newly developed radioimmunoassay technique and to evaluate this method in terms of its clinical application. For the determination of bradykinin (BK), this assay uses a rabbit anti-serum which has been injected with kallidin. This assay shows good specific activity, recovery and reproducibility. In order to avoid the formation of kinin as well as to block its inactivation, human blood samples were collected with a polypropylene syringe containing an inhibitor mixture (EDTA, trasylol, 1-10-phenanthroline, soybean trypsin inhibitor, polybrene). 1) The plasma BK concentration in normal human subjects, in patients with essential hypertension, effort angina and other cardiac diseases were 12.2, 9.2, 8.0 and 14.0 pg/ml, respectively. 2) Thirty min after captopril (12.5 mg, p.o.) administration, blood pressure and pulmonary wedge pressures decreased, and cardiac output increased accompanied with increases in plasma renin activity, plasma BK concentration and plasma norepinephrine concentration. 3) During the cold pressor test, both plasma BK concentration and blood pressure increased in the normal human subjects, whereas plasma BK levels decreased and blood pressure increased in the patients with hypertension. This radioimmunoassay for plasma BK determination makes it possible to measure plasma BK concentration in patients with various cardiac diseases.
 ...
PMID:[Plasma bradykinin concentration in patients with cardiovascular diseases]. 636 31


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>