Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. Bradykinin (0.02-5 microgram) applied to the epicardium of the left ventricle in the open-chest, anaesthetized dog, elicits dose-related reflex pressor effects and acceleration of the heart rate. 2. Bradykinin-induced reflex tachycardia was suppressed after the blockade of beta-adrenoceptors with propranolol, whereas reflex pressor responses were prevented by blocking the alpha-adrenoceptor sites with phenoxybenzamine. 3. Vagotomy and atropine treatment did not affect reflex hypertension and tachycardia to epicardial bradykinin. 4. After spinal section at C1, the pressor responses to epicardial bradykinin were significantly reduced, but still present in all but one experiment. A small acceleration of the heart occurred in two out of five spinal dogs with intact vagi and was absent in three vagotomized spinal dogs. 5. The results indicate the reflex activation of the sympathetic outflow to the heart and blood vessels, mediated mainly at a supraspinal level as a predominant mechanism for the cardiovascular response initiated by bradykinin-induced stimulation of cardiac pain receptors.
 ...
PMID:Sympathetic cardiovascular reflex initiated by bradykinin-induced stimulation of cardiac pain receptors in the dog. 26 62

Plasma kallikrein releases bradykinin when activated by gram-negative septicemia or irreversible hemorrhagic shock. Pancreatitis releases glandular kallikrein causing hypotension and increased vascular permeability. Bradykinin in the brain produces hypertension. Renal kallikrein is released by high arterial pressure, vasodilators, low doses of noradrenaline, angiotensin II, mineralocorticoids and rapid volume expansion. It has a biphasic relation to sodium excretion. In essential hypertension, kallikrein release into the blood and urine is low and facilitates hypertension. High renin in Bartter's syndrome is balanced by high PGE and kallikrein without hypertension.
 ...
PMID:Kallikrein, kininogen and kinins in control of blood pressure. 37 13

Nitric oxide (NO) plays an important role in the regulation of coronary vascular resistance. The aim of the present study was to evaluate the role of NO in the regulation of coronary vascular resistance in isolated hearts from normo- and hypertensive rats, which served as a model for arterial hypertension and hypertensive heart disease. Isolated hearts from normotensive Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHRs) were perfused at constant flow, whereas the release of NO into the coronary circulation was measured simultaneously by the oxyhemoglobin technique. Bradykinin, an endothelium-dependent vasodilator, concentration-dependently decreased the coronary perfusion pressure in SHRs by 47 +/- 3% and in WKY rats by 35 +/- 6%. In parallel, the basal NO release increased in both groups, maximally by 154 and 118 pmol/min in SHRs and WKY rats, respectively. Amounts of released NO were sufficient to account for the bradykinin-induced coronary vasodilation. These data indicate that coronary resistance vessels in hearts from hypertensive compared to normotensive rats exhibit a higher sensitivity to the endothelium-dependent vasodilator bradykinin, paralleled by a higher release of NO into the coronary circulation. An enhanced endothelial NO synthesis within the coronary circulation may represent a compensatory mechanism aimed at counterregulating distinct changes in vascular reactivity occurring in arterial hypertension.
 ...
PMID:The role of nitric oxide in the regulation of coronary vascular resistance in arterial hypertension: comparison of normotensive and spontaneously hypertensive rats. 128 63

Bradykinin caused graded contractions of rings of rabbit aorta and jugular vein with EC50 values of 1.3 microM and 2.2 nM. In denuded preparations, responses of bradykinin in jugular vein but not in aorta were potentiated 1,000-fold. Both preparations bathed in calcium-free solution showed markedly depressed responses to bradykinin, but addition of 1 mM EGTA further inhibited bradykinin responses only in aorta. Time-course experiments carried out in calcium-free solution plus EGTA revealed that bradykinin contractions in rabbit aorta were very sensitive to extracellular calcium, whereas responses of the jugular vein depended on both extracellular and intracellular calcium sources. Responses to bradykinin in both tissues were unaffected by nicardipine (1 microM) but were partially antagonized by NiCl2 (0.1-0.3 mM). Ryanodine (30 microM) incubated in calcium-free medium markedly inhibited jugular vein responses to bradykinin but had no effect on aortic responses. Phorbol ester (1 microM) caused a slow tonic contraction in jugular vein but not in aorta and inhibited bradykinin responses in the former preparation. Staurosporine (1-100 nM) and 1-(5-isoquinolinesulfonyl)-2-methylpiperizine (H-7, 3 and 10 microM) caused a dose-dependent inhibition of bradykinin-induced contractions in jugular vein but were less effective in aorta.(ABSTRACT TRUNCATED AT 250 WORDS)
Hypertension 1992 Feb
PMID:Effect of protein kinase C and calcium on bradykinin-mediated contractions of rabbit vessels. 131 Apr 85

1. The kinin antagonist des-Arg9-[Leu8]bradykinin, injected into the lateral ventricle, caused a long-lasting, dose-dependent reduction in arterial blood pressure and heart rate in spontaneously hypertensive rats but not in normotensive Wistar-Kyoto rats; the antagonist also blocked the pressor response to ventricularly infused bradykinin in both strains. 2. Bradykinin content was increased in the hypothalamus and septum and decreased in the dorsal medulla of spontaneously hypertensive rats when compared with those of normotensive Wistar-Kyoto rats, whereas similar bradykinin contents were observed in the pineal gland, hypophysis and rostroventrolateral medulla of both rat strains. 3. Increased concentrations of bradykinin and its precursor kininogen were found in the cerebrospinal fluid of spontaneously hypertensive rats. 4. Bradykinin receptor numbers, measured as the binding of [125I-Tyr1]bradykinin to nervous tissue, were found to be increased in the dorsal medulla and hypophysis, and to be decreased in the pineal gland, of spontaneously hypertensive rats. 5. Therefore, the central kinin system may participate, by both pre- and post-synaptic mechanisms, in the maintenance of hypertension in spontaneously hypertensive rats.
 ...
PMID:Central bradykininergic system in normotensive and hypertensive rats. 131 60

The contribution of endogenous kinins to the chronic antihypertensive effect of angiotensin converting enzyme inhibitors was investigated in two-kidney, one clip hypertensive Wistar rats, using the new bradykinin B2-receptor antagonist HOE 140 (D-Arg, [Hyp3, Thi5, D-Tic7, Oic8]-bradykinin). In a first protocol, rats were pretreated orally with the angiotensin converting enzyme inhibitor ramipril (1 mg/kg per day), for 4 weeks. Acute blockade of bradykinin receptors by intravenous injections of HOE 140 at doses of 8.4 and 100 micrograms/kg, which inhibited the depressor responses to exogenous bradykinin, did not affect the antihypertensive effect of ramipril in these animals. Bradykinin receptors were then blocked chronically by subcutaneous infusion of HOE 140 (500 micrograms/kg per day) via osmotic minipumps for 6 weeks, while ramipril treatment was continued. HOE 140 partially reversed the antihypertensive effect of ramipril from 115.3 +/- 4.6 to 123.8 +/- 3.3 mm Hg (mean arterial blood pressure) after 3 weeks and to 121.3 +/- 2.9 mm Hg after 6 weeks. In contrast, in controls (ramipril plus subcutaneous vehicle infusion) mean arterial blood pressure decreased further from 112.0 +/- 6.0 to 110.3 +/- 4.9 mm Hg after 3 weeks and to 103.7 +/- 5.0 mm Hg after 6 weeks (p less than 0.05 and p less than 0.01, HOE 140 versus controls). Plasma catecholamines were not significantly different between the two groups at the end of the experiment, indicating that the partial reversal of the antihypertensive effect was not due to a bradykinin-like agonistic effect on catecholamine release.(ABSTRACT TRUNCATED AT 250 WORDS)
Hypertension 1992 Jul
PMID:Chronic kinin receptor blockade attenuates the antihypertensive effect of ramipril. 131 60

In our studies, we investigated the vasodepressor effects of bradykinin in vivo in normotensive and hypertensive subjects. Bradykinin was injected intravenously and intra-arterially (40-6,050 pM/kg) and was infused intra-arterially (40-6,050 pM/kg/min). The investigations were performed in 21 normotensive and 15 hypertensive patients. Bradykinin injections were performed after the following pharmacological interventions: salt restriction (10 mmol of Na/day), salt loading (300 mmol of Na/day), captopril (50 mg), ramipril (5 mg), lisinopril (20 mg), ketotifen (2 X 1 mg), indomethacin (2 X 50 mg), and propranolol (80 mg). The results show that bradykinin lowers blood pressure in a dose-related manner by marked reduction in peripheral vascular resistance. The blood pressure reduction was strongly correlated with the increase in kinin concentration. This effect of bradykinin appears to be independent of changes in sodium metabolism, beta-adrenoceptors, histamine-1 receptors, and prostaglandins. ACE inhibitors protentiate the blood pressure-lowering effect of bradykinin approximately 20- to 50-fold. In the case of intra-arterial injection of bradykinin, only 2-5% of the intravenously used dose of bradykinin are needed to produce an identical fall in blood pressure. From these experiments, a pulmonary clearance rate of bradykinin of over 95% can be calculated. In the pulmonary arteries, bradykinin has no effect on vascular resistance. In patients suffering from primary or renovascular hypertension, the blood pressure response to bradykinin was enhanced. The bradykinin potentiating effect of the ACE inhibitors was not altered in the hypertensives. In patients suffering from borderline hypertension or primary hyperaldosteronism, bradykinin caused the same blood pressure lowering effect as in the normotensives.
 ...
PMID:Hemodynamic effects of bradykinin on systemic and pulmonary circulation in healthy and hypertensive humans. 169 61

Inhibitors of the angiotensin-converting enzyme (ACE = kininase II) by definition have a dual action: prevention of angiotensin II generation and inhibition of kinin degradation. Although the first mechanism is generally accepted, it may not by itself be sufficient to explain the acute blood pressure-lowering action of these compounds. Studies in experimental and clinical hypertension, including the use of selective angiotensin II and bradykinin receptor antagonists, suggest additional vasodilator, non-renin-dependent mechanisms in their action on blood flow and blood pressure. Inhibition of kinin degradation by ACE inhibitors will amplify kinin-mediated reactions on local vessel tone, in particular, if kinin generation is stimulated or this situation is experimentally mimicked by addition of exogenous bradykinin. The acute blood pressure-lowering action of ACE inhibitors is inhibited by indomethacin-type cyclooxygenase inhibitors, suggesting a contribution of bradykinin-induced release of vasodilator prostaglandins to their action. Bradykinin stimulates the phospholipase-dependent release of arachidonic acid from membrane phospholipids, allowing for subsequent generation of its metabolites, the eicosanoids. This stimulation is receptor-mediated and involves one or more types of B2 receptors, coupled via G-proteins to intracellular messenger systems that control cytosolic calcium levels. Bradykinin-induced changes in vessel tone are transient, caused by a rapidly developing tachyphylaxis at the receptor level. The potent vasodilator action of systemic bradykinin administration is not consistently reflected in studies performed on isolated blood vessels. This is probably due to the indirect nature of kinin-mediated vasomotor responses, i.e., the release of vasoactive mediators, most notably the eicosanoids and endothelium-derived relaxing factor (EDRF).(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Converting enzyme inhibitors and the interaction between kinins and eicosanoids. 169 63

Bradykinin is a potent vasodilator peptide; however, its half-life in vivo is very short because of various plasma and tissue peptidases that hydrolyze bradykinin to inactive fragments. We studied the role of kininase II (angiotensin converting enzyme) and neutral endopeptidase 24.11 (enkephalinase) in the catabolism of bradykinin in vascular tissue by determining the effect of inhibitors of kininase II (captopril) and of endopeptidase 24.11 (phosphoramidon) on the action of bradykinin on rat isolated mesenteric arteries. Because bradykinin may induce prostaglandin formation and release, we also studied the effect of a cyclooxygenase inhibitor, indomethacin, on the action of bradykinin. The mesenteric bed was isolated from rats (250-300 g) with rats under either anesthesia and was perfused with Krebs' solution (4 ml/min) containing phenylephrine (0.5-1.0 microgram/ml) to produce a mean perfusion pressure of 120-130 mm Hg. Bradykinin (2.5-40.0 ng), injected as a bolus, produced a dose-dependent decrease in perfusion pressure. In the presence of indomethacin (1.0 microgram/ml), the amplitude of the vasodilator responses to bradykinin was not significantly affected, although the duration of the responses was increased approximately two to four times. In the presence of captopril (1.0 microgram/ml), bradykinin elicited either a vasodilator or a biphasic effect. The vasodilator effect was greatly potentiated by captopril, whereas the duration of the response was unchanged when compared with control experiments. When present, the pressor responses were also dose related. In the presence of indomethacin plus captopril, bradykinin produced only a fall in perfusion pressure that lasted five to six times longer than without any treatment.(ABSTRACT TRUNCATED AT 250 WORDS)
Hypertension 1992 Feb
PMID:Effect of bradykinin on isolated mesenteric arteries of the rat. 173 87

The goal of this study was to determine whether responses of the basilar artery are altered during chronic hypertension. We measured the diameter of the basilar artery using intravital microscopy in normotensive Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR). Acetylcholine (10 microM) dilated the basilar artery by 25 +/- 4% (means +/- SE) in WKY but by only 2 +/- 2% in SHR. Bradykinin (1.0 microM) dilated the basilar artery by 12 +/- 1% in WKY, but did not alter diameter in SHR (-0.1 +/- 2%). In contrast, nitroglycerin produced similar vasodilatation in WKY and SHR. Next, we examined the possibility that impaired vasodilatation in SHR may be related to the production of a cyclooxygenase constrictor substance. Indomethacin (10 mg/kg iv) did not restore vasodilatation in response to acetylcholine and bradykinin in SHR. Finally, we examined the role of nitric oxide in dilatation of the basilar artery in response to acetylcholine and bradykinin in WKY. NG-Monomethyl-L-arginine (L-NMMA; 1.0 microM) had little effect on baseline diameter but inhibited vasodilation in response to acetylcholine and bradykinin. Vasodilatation in response to nitroglycerin was not altered by L-NMMA. These findings suggest a profound impairment of endothelium-dependent dilatation of the basilar artery during chronic hypertension. In addition, impaired vasodilatation is not related to the production of a cyclooxygenase constrictor substance. Furthermore, dilatation of the basilar artery in WKY in response to acetylcholine and bradykinin appears to be related to the production of nitric oxide or a substance capable of liberating nitric oxide.
 ...
PMID:Impairment of endothelium-dependent dilatation of basilar artery during chronic hypertension. 212 45


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