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

To investigate whether altered renal medullary prostaglandin (PG) synthesis is involved in the development of hypertension in spontaneously hypertensive rats (SHR), we compared the capacity of PGE2 synthesis in cultured renal papillary collecting tubule cells from young (4-week-old) and aged (16-week-old) SHR and control Wistar-Kyoto rats (WKY). Basal levels of PGE2 synthesis were lower in young SHR cells than in WKY cells (p less than 0.001). Arachidonic acid-stimulated PGE2 synthesis, however, had a slight tendency to be higher in SHR cells than in WKY cells. Bradykinin- and A23187-stimulated PGE2 synthesis were similar in both strains. Basal levels of cyclic AMP were also lower in young SHR cells than in WKY cells (p less than 0.001), but the cAMP response to exogenous PGE2 was equal between the strains. In papillary collecting tubule cells from aged rats, basal levels of PGE2 and cyclic AMP as corrected for cellular protein were significantly lower than those in young rats, but there was no difference between the strains. Urinary excretion of PGE2 and thromboxane B2 was equal in aged SHR and WKY. These results suggest that papillary collecting tubule of young SHR and WKY may differ in the metabolism of PGE2 and cyclic AMP. This difference may be attributed to the possible defect in arachidonate availability in SHR.
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PMID:PGE2 synthesis in cultured renal papillary collecting tubule cells from young and aged spontaneously hypertensive rats. 248 50

In our studies we investigated the vasodepressor effects of bradykinin in vivo in normotensive and hypertensive subjects. Bradykinin was injected intravenously and intraarterially (40-6050 pM/kg) respectively was infused intraarterially (40-6050 pM/kg/min). The investigations were performed in 21 normotensives and 15 hypertensives. Bradykinin injections were performed after the following pharmacological interventions: salt restriction (10 mmol Na/d), salt loading (300 mmol Na/d), 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 dose related 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, of beta adrenoceptors, of histamine-1 receptors, and of prostaglandins. ACE-inhibitors potentiate the blood pressure lowering effect of bradykinin about 20- to 50-fold. In case of an intraarterial injection of bradykinin in only 2-5% o the intravenously used dose of bradykinin are needed to produce an identical fall in blood pressure. From this experiments a pulmonary clearance rate of bradykinin over 95% can be calculated. In the pulmonary arteries bradykinin has no effect on the 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 bradykinin hypertension or primary hyperaldosteronism bradykinin developed the same blood pressure lowering effect as in the normotensives.
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PMID:[Effect of bradykinin on systemic and pulmonary hemodynamics in the human]. 258 15

These experiments were designed to assess the interaction of bradykinin and its antagonist (Arg-Pro-Hyp-Gly-Phe-Ser-DPhe-Phe-Arg-trifluoroacetic acid) with the sympathoadrenal system. Three groups of male Wistar rats received 5-minute intra-arterial infusions of either dextrose (Group 1, n = 6), bradykinin, 250 micrograms/min (Group 2, n = 5), or bradykinin, 25 micrograms/min (Group 3, n = 4). Six other groups received a similar infusion of the bradykinin antagonist at 250 micrograms/min. They were either intact rats (Group 4, n = 10) or rats previously submitted to chemical sympathectomy (Group 5, n = 17), to adrenal enucleation (Group 6, n = 8), to combined alpha-adrenergic and beta-adrenergic blockade (Group 7, n = 7), to alpha 1-adrenergic receptor blockade (Group 8, n = 8), or to alpha 2-adrenergic receptor blockade (Group 9, n = 8). Bradykinin infusion produced a sustained fall in mean arterial pressure (MAP) in Groups 2 and 3 (by -48 +/- 3 and -36 +/- 7 mm Hg, respectively) associated with similar increases in plasma epinephrine levels (100-fold), and norepinephrine (sevenfold) as compared with Group 1. The bradykinin antagonist infusion in intact rats produced a 23 +/- 4 mm Hg rise in MAP associated with a sixfold increase in epinephrine and a twofold increase in norepinephrine. Group 5 rats with lower baseline catecholamine levels had an even larger MAP rise (30 +/- 6 mm Hg) accompanied by a rise in epinephrine and norepinephrine proportionally similar to that of intact animals.(ABSTRACT TRUNCATED AT 250 WORDS)
Hypertension 1988 Jun
PMID:Vascular and sympathoadrenal responses to bradykinin and a bradykinin analogue. 289 59

Assessment of the effects of pharmacologic agents on renal blood flow (RBF) is clinically important in many disease states, including hypertension and congestive heart failure. However, because of the complexities of RBF, quantitation in vivo has been technically difficult. This study demonstrates the utility of ultrasound imaging of the kidney combined with injection of a sonicated radiocontrast solution (Renografin-76) for the assessment of regional renal blood flow. The technique uses a suspension of uniform microbubbles (diameter 4.4 +/- 2.8 micron), which when injected directly into the descending aorta are distinctly visualized by renal ultrasound. Five dogs were studied. Catheters were placed in the descending aorta for injection of sonicated Renografin and in the renal artery for drug infusions. Data were collected before and during intrarenal artery infusions of bradykinin and norepinephrine. Total RBF was measured by electromagnetic flowmeter. Video density time curves were generated for comparable segments of the outer renal cortex and fit to a monoexponential decay curve. This allowed calculation of the mean exponential decay index (t1/2). An increase in t1/2 paralleled decreased renal perfusion (i.e., longer washout of contrast material). The opposite was true for a decrease in t1/2. Bradykinin increased RBF from 134 +/- 26 to 249 +/- 19 ml/min (p less than .01 vs control), and norepinephrine decreased RBF from 130 +/- 25 to 51 +/- 17 ml/min (p less than .01 vs control).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Contrast ultrasonography of the kidney: a new method for evaluation of renal perfusion in vivo. 353 95

Bradykinin is an endogenous inflammatory mediator, and its mechanism of action is incompletely understood. It is controversial whether bradykinin causes a sustained increase in microvascular permeability, or has only a transient effect. In anesthetized dogs intraarterial infusion of bradykinin (0.14 to 0.54 micrograms/kg/min) produced an immediate increase in flow of protein-rich, hindpaw lymph. After 210 min of bradykinin infusion lymph flow was threefold greater than baseline, lymph protein concentration remained doubled, and in a dose-related fashion bradykinin produced a sustained increase in lymph protein flux. Lymph flow was then further increased with venous hypertension, and after 4 hr lymph protein flux remained greater from the bradykinin paws than from the control paws. This sustained increase in protein flux indicates that bradykinin produces an increase in permeability at the microvascular membrane by a mechanism that is different from how the initial increase in permeability was produced.
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PMID:Bradykinin causes a prolonged increase in skin microvascular permeability. 374 90

Polypeptides are endogenous agents, involved in the regulation of many physiologic functions and the pathogenesis of several diseases. Polypeptide antagonists form a group of new chemical entities which may provide valid therapeutic agents. Some polypeptides (angiotensin, kinins) are released through the action of proteolytic enzymes (renin, kallikreins) and act as hormones or autacoids; others (substance P, neurotensin) are synthetized by nervous cells to serve as neurotransmitters or neuromodulators. The main homeostatic role of the renin-angiotensin system is to uphold high systemic arterial blood pressure. Overproduction of renin and insufficient checking of renin secretion are among the most common causes of arterial hypertension. Several forms of arterial hypertension (neurovascular, idiopathic) benefit from a reduction in renin-angiotensin system activity. This is achieved either through decreasing renin secretion, by inhibiting conversion of angiotensin I into angiotensin II, or through blocking the peripheral actions (at the receptor sites) of angiotensin II. Renin secretion is very significantly reduced by beta-blocking agents (propranolol); conversion of angiotensin I into angiotensin II is inhibited by teprotide, captopril and their derivatives; peripheral actions of angiotensin II are blocked by saralasin. Bradykinin and related agents produce vasodilation, increase vascular permeability and stimulate pain fibers. Kinins thus reproduce the cardinal features of inflammation and are held to be mediators of the inflammatory reaction. The substance P neuropeptide is found in the brain and bowel; it may act as a transmitter of the sensation of pain at the spinal cord and central nervous system sites. Among other effects outside of the brain, substance P is a potent vasodilator and inhibits renin secretion. Neurotensin is a neuropeptide which produces hypothermia, muscular relaxation and analgesia. Outside of the brain, this peptide is involved in the regulation of gastric secretion, intestinal motility and insulin and glucagon secretion. The vasoactive intestinal peptide, found in certain cholinergic nerve endings, is a large peptide which inhibits gastric secretion, intestinal motility and vascular tone.
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PMID:[Polypeptides and antagonists]. 620 6

Captopril, an inhibitor of angiotensin converting enzyme, was administered twice daily to 13 hypertensive patients for a mean period of 9 weeks. Continuous blood pressure control in the ambulatory patients was established with a portable blood pressure recorder. Notwithstanding, in eight patients with normal renal function, plasma converting enzyme was found to resume normal activity before administration of the morning dose of captopril. Only in 5 patients with impaired renal function did some blockade of plasma converting enzyme persist for more than 12 hours. Measured plasma converting enzyme activity seemed to reflect total conversion of angiotensin I, including conversion in the pulmonary vascular bed, since changes in its activity were closely paralled by changes in plasma aldosterone levels. Bradykinin accumulation seems unlikely when converting enzyme and thus, presumably, kininase II has resumed normal activity. Captopril administration does not seem to alter plasma epinephrine or norepinephrine levels. Blood pressure reduction in the face of normal angiotensin converting enzyme activity is probably due to hyporesponsiveness of the arterioles to pressor hormones, which may be due to specific renin-related and/or nonspecific effects of captopril.
Hypertension
PMID:Discrepancy between antihypertensive effect and angiotensin converting enzyme inhibition by captopril. 624 69

Bradykinin (BK) produced concentration-related relaxations of cat middle cerebral arteries and was ineffective in cat basilar arteries. On rabbit basilar arteries, BK initially produced concentration-related relaxations; however, when repeated at 2-hour intervals, BK eventually produced pure contractile responses. After preincubation of the tissues with cycloheximide, BK produced reproducible relaxation responses. The angiotensin-converting enzyme inhibitors, SQ 14,225, BPP5a, and BPP9a, had no effect on the concentration-effect curves of BK, AII, or 5-HT with any of the preparations, but responses to AI were inhibited. These results suggest that, in these tissues, angiotensin-converting enzyme is important for conversion of AI to AII, but apparently not for the degradation of BK.
Hypertension
PMID:Angiotensin-converting enzyme, bradykinin, angiotensin, and cerebral vessel reactivity. 631 57

The influence of different doses of bradykinin (2.5 micrograms, 5 micrograms/kg i.v.) and dopamine (0.5 micrograms - a small dose and 25 micrograms, 250 micrograms/kg i.v. - a big dose) administered into the rat femoral artery on the blood pressure was estimated. Dopamine evoked hypotension (the small dose) or hypertension (the big dose). Bradykinin evoked dose-dependent decrease of the blood pressure. Bradykinin (2.5 micrograms/kg i.v.) administered in the 45th sec of the dopamine action enhanced the hypertensive effect and decreased the hypotensive effect of dopamine. Dopamine administered in the big dose after phentolamine and propranolol evoked hypotension. This effect was stronger after administration of dopamine (25 micrograms/kg i.v.). The hypotensive action of bradykinin persisted in spite of phentolamine and propranolol application but this peptide did not change the hypotensive effect of dopamine under these conditions. The authors discuss hypothetical mechanism of action of the observed influence of bradykinin on the effect of dopamine in the circulatory system.
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PMID:Examinations on contribution of bradykinin in the action of dopamine in circulatory system of rats. I. Influence of bradykinin in the action of dopamine on arterial blood pressure of rats. 667 75

1. The peptide converting enzyme inhibitor captopril was given (1.25 mg/kg intravenously) to normal and nephrectomized rats and rats with renovascular and deoxycorticosterone hypertension. 2. Captopril lowered blood pressure to a small extent in normal and nephrectomized rats. Bradykinin infusion in nephrectomized animals, however, potentiated the vasodepressor action of captopril. 3. Captopril produced a major blood pressure fall in the early stages of Goldblatt two-kidney one-clip hypertension: even when hypertension had been present for more than 4 months, a substantial vasodepressor action was seen. Rats with deoxycorticosterone-induced hypertension also showed a significant blood pressure fall. 4. Captopril was given to salt-loaded and salt-depleted rats in which the renin-angiotensin system had been blocked by infusion of the competitive angiotensin II antagonist saralasin. Captopril still lowered blood pressure in the salt-depleted group. 5. Captopril lowers blood pressure in situations where the renin-angiotensin system is not responsible for blood pressure maintenance. Further, the fall in blood pressure produced in Goldblatt two-kidney one-clip hypertension is greater than would be predicted on the basis of renin-angiotensin blockade. It is likely therefore that captopril lowers blood pressure by an action additional to angiotensin blockade. Bradykinin potentiation is one possible mechanism by which this may take place.
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PMID:Vasodepressor property of the converting enzyme inhibitor captopril (SQ 14 225): the role of factors other than renin-angiotensin blockade in the rat. 698 24


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