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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hypertension and hypercholesterolemia predispose to atherosclerosis. Ramipril, known to lower blood pressure, was used to study the effect of converting-enzyme inhibition on impairment of endothelium-derived relaxation and changes in basal cGMP content in rabbits fed an atherogenic diet (0.25% cholesterol). The generation of cGMP in the presence of bradykinin and ramiprilat was studied in vitro in aortic segments from normal untreated rabbits as well as in bovine endothelial cells. The ability to relax in response to acetylcholine was almost abolished in aortic segments from the vehicle-treated rabbits fed the atherogenic diet for 4 months. The basal cGMP content was substantially reduced. Aortic segments from rabbits concomitantly treated with ramipril (0.3 and 3.0 mg/kg/day) for 3 months showed well-preserved relaxation and matching basal cGMP content compared to normal controls. The relaxation was not significantly greater in aortic segments from ramipril-treated rabbits fed the standard diet, but the cGMP content was more than doubled. In vitro studies in aortic segments and in endothelial cells showed that both the ramiprilat and bradykinin concentrations dependently stimulated cGMP formation, which serves as a biochemical marker of nitric oxide or EDRF release. Thus, the observed endothelial protection against hypercholesterolemia by ramipril may be the result of continuously increased cGMP formation due to preserved EDRF release. This is presumably produced by enhanced bradykinin activity through inhibition of degradation by converting-enzyme inhibition with ramipril.
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PMID:Preservation of endothelial function by ramipril in rabbits on a long-term atherogenic diet. 172 17

Kinins are present in the central nervous system, and central administration of bradykinin increases blood pressure and heart rate. In this study, we determined the effect of intracerebroventricular infusion of bradykinin on the baroreceptor reflex of conscious rats. Male Wistar rats were anesthetized with thiobarbital (40 mg/kg i.p.), and chronic intracerebroventricular cannulas (25 gauge) were implanted into the lateral ventricles. Baroreceptor control of heart rate was evaluated by recording reflex heart rate changes (beats per minute) in response to mean arterial pressure changes (mm Hg) produced by bolus injection of phenylephrine (0.5-20 micrograms/kg i.v.) or sodium nitroprusside (0.5-25 micrograms/kg i.v.). The ratio beats per minute/mm Hg or the mean slope of the individual regression lines of the relation between heart rate and mean arterial pressure changes for increases or decreases in arterial pressure was used as an index of baroreceptor reflex sensitivity. Baroreceptor control of heart rate was evaluated within 1 and 3 hours of intracerebroventricular infusion of bradykinin (7.5 micrograms/7 microliters/hr) or saline (7 microliters/hr). There was no change in basal mean arterial pressure or heart rate during central bradykinin infusion (112 +/- 2 mm Hg and 402 +/- 18 beats per minute in the control period). After 1 hour of central bradykinin infusion, there was a significant increase of baroreceptor reflex sensitivity for increments in mean arterial pressure (-2.91 +/- 0.26 versus -1.5 +/- 0.24 beats per minute/mm Hg in the control period; p less than 0.01, paired Student's t test). In contrast, no significant changes were observed for the reflex tachycardia. Similar results were obtained with 3 hours of infusion.(ABSTRACT TRUNCATED AT 250 WORDS)
Hypertension 1992 Feb
PMID:Centrally infused bradykinin increases baroreceptor reflex sensitivity. 173 75

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

We assessed the vasodilator effect of endothelium-derived nitric oxide by inhibiting its formation with NG-monomethyl L-arginine (LNMMA) on systemic and regional hemodynamics in conscious, normotensive rats, using the radioactive microsphere technique. In rats injected with 10 mg/kg LNMMA (n = 8), mean blood pressure increased by 16.2 +/- 2.6 mm Hg, and heart rate decreased by 54.3 +/- 16.7 beats per minute. In comparison with rats injected with 5% dextrose (n = 14), cardiac index was lower by 35.6% (p less than 0.01), and total peripheral vascular resistance was higher by 51.6% (p less than 0.01); regional blood flows were lower and vascular resistance higher in most organs. Changes were significant in the heart, kidney, stomach, large intestine, skin, and adrenals (p less than 0.05). Preinjection of 100 mg/kg L-arginine prevented the pressor response but only partially attenuated the other hemodynamic effects of LNMMA. Combination of LNMMA with the bradykinin antagonist (D-Arg-Arg-Pro-Hyp-Gly-Thi-Ser-D-Phe-Thi-Arg)trifluoroacetic acid (50 micrograms/min for 5 minutes) did not produce systemic or regional effects different from those obtained with LNMMA alone. Combination of LNMMA with indomethacin (10 mg/kg) resulted in additional changes in the cerebral circulation, blood flow decreasing by an additional 44.2% (p less than 0.01) and vascular resistance increasing by 75.3% (p less than 0.01) compared with changes produced by LNMMA alone.(ABSTRACT TRUNCATED AT 250 WORDS)
Hypertension 1992 Feb
PMID:Inhibition of nitric oxide, bradykinin, and prostaglandins in normal rats. 173 88

In rings of rat portal vein, endothelin-1, endothelin-2, and endothelin-3 caused graded slow contractions and potentiated spontaneous contractions. The apparent EC50 values and maximal responses to 30 nM endothelin were 1.4 nM and 0.96 g for endothelin-1, 5.2 nM and 0.65 g for endothelin-2, and 1.7 nM and 0.62 g for endothelin-3 (n = 4-12). At concentrations producing half the contraction triggered by 80 mM KCl, the order of potencies was endothelin-1 greater than U46619 = angiotensin II greater than bradykinin greater than substance P greater than phenylephrine. Longitudinal portal-mesenteric vein preparations developed very modest contractions to endothelin-1 (0.13 g at 30 nM; n = 5), but their responses to 80 mM KCl and phenylephrine were greater than those of rings. Responses of rings to endothelin-1 were profoundly reduced in Ca(2+)-free medium, but less inhibition was obtained after incubation with nicardipine (up to 1 microM) and/or nickel (up to 0.5 mM), phorbol (up to 0.3 microM), staurosporine (up to 10 nM), or cromakalim (3 microM). Indomethacin (5.6 microM) did not affect responses to endothelin-1. Cromakalim (0.1-3 microM) also relaxed rings constricted with 0.3 nM endothelin-1, and this effect was partially reversed by glibenclamide (3 microM). Thus, endothelins, especially endothelin-1, are potent constrictors of portal vein rings but not of portal-mesenteric vein strips. Their action appears to rely largely on Ca2+ influx from the external medium (only in part via L- and T-type Ca2+ channels) and activation of protein kinase C but not on eicosanoid generation.(ABSTRACT TRUNCATED AT 250 WORDS)
Hypertension 1992 Feb
PMID:Potent constrictor actions of endothelin-1, endothelin-2, and endothelin-3 in rat isolated portal vein. 173 99

Late diabetic effects are the sequelae of for a long time super elevated blood sugar levels. The diabetic nephropathy is the cause of the secondary arterial hypertension. The investigation seeks for the connections between the diabetes mellitus and the essential, that is primary hypertension. The two diseases frequently appear and clearly increase in the second half of life. Moreover, they are above average frequently associated with each other. Among brothers and sisters of diabetic hypertensives in comparison to normal cohorts clearly increased high blood pressure prevalences were found. The insulin resistance which could be proved in a great number of hypertensive and which has been known since more than two decades might be the connecting link between hypertension and diabetes mellitus. Like the obesity the essential hypertension can be associated with all degrees of an insulin hyposensitiveness. The sodium-retaining effect of the insulin might explain the increased sodium content of the body in hypertensives. The differential diagnostics of the essential hypertension should therefore seek for conditions of an insulin resistance. The type II diabetic lacks a release of bradykinin during muscle work. Thus the glucose uptake into the cell is unfavourable influenced and demands an increased insulin excretion. This genetically (?) fixed defect is found also in essential hypertensives. It could be the connecting link between the two diseases. ACE-inhibitors have via a kininase II inhibition an effect also on the bradykinin decomposition and can favourable influence the glucose uptake into the muscle. An improved insulin effect among the ACE-inhibitors was described. Therefore, they should be preferred in the treatment of hypertensive diabetics.
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PMID:[Diabetes mellitus and arterial hypertension. In search of the connecting link]. 177 26

Thirty-seven compounds were tested as antagonists of kinin B2- and B1-receptors to identify the chemical changes required to obtain antagonism, improve antagonist affinity, and eliminate residual agonistic activities. Apparent affinity of antagonists was evaluated in terms of pA2 on the rabbit jugular vein, the dog carotid and renal arteries, the hamster urinary bladder, the guinea pig ileum, the rat vas deferens, the guinea pig trachea, and the rabbit aorta, using bradykinin and desArg9-bradykinin as B2- and B1-receptor activators. Replacement of Pro7 of bradykinin with D-Phe leads to antagonism; substitution of Pro3 by Hyp and extension of the peptide chain at the N-terminal with a D-Arg residue improves the affinity of antagonists; acetylation of N-terminal amine function reduces residual agonistic activity; these changes, combined with the replacement of Phe8 by Leu as in Ac-D-Arg[Hyp3,D-Phe7,Leu8]-bradykinin, led to potent full B2-receptor antagonists. Affinity of antagonists differs markedly between highly sensitive (rabbit jugular vein, dog carotid and renal artery), moderately sensitive (hamster urinary bladder, guinea pig ileum, and rat vas deferens), and insensitive preparations (the guinea pig trachea) in which antagonists act as potent stimulants. High concentrations of antagonists block bradykinin completely in the rabbit jugular vein but not in the guinea pig ileum, suggesting that kinins stimulate the moderately sensitive tissues by two mechanisms, of which only one is blocked by antagonists. It thus appears that kinins act on various B2-receptor subtypes or by different action mechanisms.
Hypertension 1991 Jan
PMID:Structure-activity studies of bradykinin and related peptides. B2-receptor antagonists. 184 19

This study was conducted to examine the role of bradykinin in the persistence of the renal vasodilator effect of captopril during angiotensin II receptor blockade. Blood pressure and renal blood flow were monitored in eight groups of pentobarbital-anesthetized rabbits. In group 4, captopril alone was administered, and it decreased blood pressure by 14 +/- 4 mm Hg and increased renal blood flow by 21 +/- 4 ml/min. After a bolus injection and a constant intravenous infusion of the imidazole derivative angiotensin II receptor antagonist DuP 753 (group 5), captopril decreased blood pressure by 9 +/- 2 mm Hg and increased renal blood flow by 8 +/- 1 ml/min (12 +/- 1% change in renal blood flow, p less than 0.05 versus group 4). In the presence of a constant intravenous infusion of saralasin (group 6), captopril decreased blood pressure by 13 +/- 5 mm Hg and increased renal blood flow by 7 +/- 2 ml/min (17 +/- 5% change in renal blood flow, p less than 0.05 versus group 4). These results did not differ from those in group 5. During a constant intrarenal arterial infusion of a B2 bradykinin receptor antagonist, DArg0, [Hyp3-Thi5,8-DPhe7]-bradykinin (BkA) (group 7), captopril decreased blood pressure by 14 +/- 4 mm Hg and increased renal blood flow by 10 +/- 4 ml/min. Combined administration of DuP 753 intravenously and BkA intra-arterially (group 8) eliminated the effect of captopril. In group 8, captopril caused insignificant changes in blood pressure and renal blood flow. The results indicate that DuP 753 and saralasin antagonize the renin-angiotensin system to a comparable extent in vivo. Although blockade of the latter system accounted for a significant part of the increase in renal blood flow caused by captopril, the remaining component was contributed by endogenous bradykinin.
Hypertension 1991 Apr
PMID:Kinin contribution to renal vasodilator effect of captopril in rabbit. 184 1

The potent vasodilatory peptide bradykinin is cleaved at the Phe5-Ser6 bond in vitro by the metalloenzyme endopeptidase-24.15 (E.C.3.4.24.15). We now report that intravenous infusion of N-[1-(R,S)-carboxy-3-phenylpropyl]-Ala-Ala-Phe-p-aminobenzoate, a specific active site-directed inhibitor of endopeptidase-24.15, produces an immediate drop in mean arterial pressure of as much as 50 mm Hg in pentobarbital-anesthetized, normotensive rats. Arterial pressure recovers within 5 minutes. The B2 bradykinin antagonist [Arg0,Hyp3,Thi5,8,D-Phe7]-bradykinin attenuates the decrease in mean arterial pressure resulting from treatment with the inhibitor. The endopeptidase-24.15 inhibitor potentiates the hypotensive effect of intravenous bradykinin infusion, increasing the maximal effect of the peptide by 47% and increasing the potency by almost 10-fold, while the response to intra-arterial bradykinin is less affected by the inhibitor. These results support a role for endopeptidase-24.15 in the inactivation of endogenous and exogenous bradykinin and suggest a direct involvement of the enzyme in the control of blood pressure.
Hypertension 1991 Sep
PMID:Inhibition of endopeptidase-24.15 decreases blood pressure in normotensive rats. 165 69

Acetylcholine produces less dilatation of pial arterioles in stroke-prone spontaneously hypertensive rats (SHRSP) than in normotensive (WKY) rats. Responses of cerebral vessels to acetylcholine and bradykinin appear to involve different mechanisms. Our first goal was to determine whether responses of pial arterioles to bradykinin are impaired in SHRSP. Diameter of pial arterioles (20-60 microns) was measured using intravital microscopy in WKY rats and SHRSP (9-12 months old). Superfusion of bradykinin (3 x 10(-7) M) dilated pial arterioles by 35 +/- 6% (mean +/- SEM) in WKY rats, but only 21 +/- 3% in SHRSP (p less than 0.05 versus WKY rats). Both nitric oxide (5 x 10(-7) M) and nitroglycerin (10(-5) M) produced similar vasodilatation in WKY rats and SHRSP. Our second goal was to determine whether alteration of postreceptor mechanisms contributes to impairment of endothelium-dependent cerebral vasodilatation in SHRSP. Calcium ionophore A23187 (10(-5) M) produced more vasodilatation in WKY rats than in SHRSP (32 +/- 8% versus 9 +/- 4%, p less than 0.05). Responses to A23187 (10(-5) M) were inhibited by indomethacin (46 +/- 13% versus 15 +/- 5%, p less than 0.05) in WKY rats, whereas responses to A23187 (10(-6) M) were potentiated modestly by indomethacin (-3 +/- 2% versus 4 +/- 2%, p less than 0.05) in SHRSP.(ABSTRACT TRUNCATED AT 250 WORDS)
Hypertension 1991 May
PMID:Endothelium-dependent responses of cerebral blood vessels during chronic hypertension. 190 37


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