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

Little is known about the distribution of prostaglandin E2 (PGE2) and prostacyclin (PGI2) production in the canine kidney. To determine the basal and stimulated profiles of PGE2 and PGI2 production along the corticomedullary axis of the dog kidney, a slice (0.5 mm thick, 10-50 mg) was obtained from six equally spaced zones along the axis (zone 1, medullary crest; zones 2 and 3, inner medulla; zone 4, outer medulla; and zones 5 and 6, cortex) and was divided into equal halves. One half of the slice was incubated with Krebs-Ringer buffer containing arachidonic acid (6.6 x 10(-4) M), bradykinin (9.4 x 10(-6) M), or indomethacin (10(-5) M), whereas the remaining half of each slice was similarly incubated in Krebs-Ringer buffer alone. The production of PGE2 and 6-keto-PGF1 alpha (the stable metabolite of PGI2) was determined by radioimmunoassay. Under basal conditions, both PGE2 and 6-keto-PGF1 alpha were highest in the innermost zones of the inner medulla (PGE2, 3,328 +/- 549 pg/mg; 6-keto-PGF 1 alpha, 1,611 +/- 129 pg/mg) and decreased exponentially to low levels in the cortex (PGE2, undetectable; 6-keto-PGF1 alpha, 13 +/- 2 pg/mg); this production was inhibited by indomethacin. Arachidonic acid significantly increased the production of PGE2 in all zones of the kidney and the production of 6-keto-PGF1 alpha only in zones 3-6.(ABSTRACT TRUNCATED AT 250 WORDS)
Hypertension 1990 Feb
PMID:Distribution of prostaglandins E2 and 6-keto-F1 alpha production in dog kidneys. 210 67

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.
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PMID:Impairment of endothelium-dependent dilatation of basilar artery during chronic hypertension. 212 45

The contribution of endogenous kinins to the acute antihypertensive actions of the converting enzyme inhibitor ramipril was investigated in kinin-deficient Brown Norway rats and in Brown Norway-Hannover rats and Wistar rats as controls. In Brown Norway rats, urinary kinin excretion was measurable but extremely low when compared with control strains. The depressor responses to intra-arterial bradykinin injections 1) were not different between Brown Norway and Brown Norway-Hannover rats, 2) were potentiated by intravenous ramipril (60 micrograms), and 3) were attenuated by intra-arterial infusion of the bradykinin antagonist B4146 (40 micrograms/kg/min) to a similar extent in both strains. In renal hypertensive (two-kidney, one clip) Brown Norway rats, the blood pressure reductions to intravenous bolus injections of ramipril (100 micrograms) were significantly reduced both in extent and duration when compared with hypertensive Brown Norway-Hannover and Wistar rats. Intra-arterial infusion of B4146 (40 micrograms/kg/min) attenuated the depressor response to ramipril in Wistar and Brown Norway-Hannover rats but had no effect in Brown Norway rats. In contrast, all three groups showed similar depressor responses to intravenous infusions of the angiotensin II receptor antagonist saralasin. These responses were not influenced by the bradykinin antagonist. Our data support the hypothesis that kinins are important for the acute antihypertensive actions of converting enzyme inhibitors.
Hypertension 1990 Oct
PMID:Converting enzyme inhibition in kinin-deficient brown Norway rats. 214 20

When inhibitors of the renin-angiotensin system (RAS) were initially developed, they were believed to act as antihypertensive agents mainly under pathophysiological conditions, in which an elevated plasma RAS contributed to the elevation and maintenance of high blood pressure (BP). However, evidence has accumulated from studies in hypertensive patients, as well as in animals, indicating that BP could be lowered by converting-enzyme inhibitors (CEIs) independently of whether or not the plasma RAS was stimulated. Several other effects had to be considered. It was thus discovered that converting enzyme (CE) is identical with the bradykinin-degrading enzyme, kininase II, and CEIs can therefore potentiate the vasodepressor effects of bradykinin and thereby interact with the prostaglandin system. Actions of CEIs possibly unrelated to inhibition of angiotensin and kininase also need to be considered. The actions of CEIs at the tissue level (brain, heart, blood vessels, kidney, adrenal gland) and their interference with the autonomic nervous system through central and peripheral actions may under certain conditions be more important than their inhibition of the circulating hormonal plasma angiotensin II. Recent clinical and experimental studies and new insights in the molecular biology of the RAS, especially gene expression of renin and angiotensinogen in tissues of the cardiovascular system, support this view. We have found that chronic CE inhibition with substances such as captopril, quinapril and lisinopril specifically affects angiotensinogen mRNA levels in cardiovascular tissues, and has marked effects on left ventricular hypertrophy, possibly through an action on cardiac angiotensin. These findings have consequences not only for the understanding of pharmacokinetics and pharmacodynamics of CEIs but also for their practical therapeutic use.
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PMID:The role of tissue renin-angiotensin systems in hypertension and effects of chronic converting-enzyme inhibition. 216 28

We examined the role of bradykinin in the onset and/or the maintenance of blood pressure and renal blood flow in deoxycorticosterone acetate (DOCA)-salt hypertensive rats by using a competitive antagonist of bradykinin [Arg-Pro-Hyp-Gly-Thi-Ser-Dphe-Thi-Arg; Hyp, L-4-hydroxyproline; Thi, beta-(2-theinyl-L-alanine)]. The intravenous injection of the bradykinin antagonist (25, 50 and 100 micrograms) produced an increase in mean arterial pressure in all rats treated with tap water, 1% NaCl and DOCA + 1% NaCl. However, the magnitude of the increase in mean arterial pressure was significantly lower in the DOCA-hypertensive rats than in the two groups of rats drinking tap water and 1% NaCl after 4 and 6 weeks, but there was no significant difference after 2 weeks. The bradykinin antagonist induced a decrease in renal blood flow in all rats. However, the extent of the fall in renal blood flow was reduced in the DOCA-hypertensive rats compared with the control rats drinking tap water. These results suggest that endogenous bradykinin is depressed in the established phase of hypertension in DOCA-hypertensive rats. It is also suggested that endogenous bradykinin may counteract the elevation of vascular resistance in the early stages of this model.
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PMID:Role of bradykinin in the regulation of blood pressure and renal blood flow in DOCA-salt hypertensive rats. 216 14

The great discovery by Furchgott of the relaxing factor released from the endothelium (EDRF) awakened us to the necessity to reevaluate the functional importance of endothelial cells that have been chemically or physically stimulated. EDRF was first demonstrated to be released by acetylcholine, substance P, bradykinin and calcium ionophore A23187; thereafter, many substances have been found to release EDRF. This factor is quite unstable, is not produced by cyclooxygenase, and is an activator of soluble guanylate cyclase that synthesizes cyclic GMP; its action is suppressed by antioxidants via the superoxide anions produced, potentiated by superoxide dismutase and abolished by methylene blue and oxyhemoglobin. Recently, the role of lipoxygenase products in the production of EDRF was evaluated with new 5-lipoxygenase inhibitors without antioxidant activity. During the last couple of years, the actions and chemical properties of EDRF were verified to be quite similar to those of nitric oxide (NO); therefore, the hypothesis of "EDRF = NO" is widely being accepted. NO is produced from L-arginine via catalysis by an enzyme that is activated by Ca2+. The enzyme activity is inhibited by L-monomethyl arginine and other L-arginine analogs. Chemical and physical stimulations increase intracellular Ca2+ in endothelial cells that seems to be associated with K(+)-channel opening and hyperpolarization. Current interests are directed to the possible roles of NO in the regulation of nerve function. There are evidences suggesting that NO modulates adrenergic nerve function in blood vessels and some brain cell functions regulated by cellular cyclic GMP. Particularly, NO may be a transmitter substance in non-adrenergic, non-cholinergic vasodilator nerves innervating the cerebral arteries. Future investigations will determine the physiological roles of EDRF or NO and its relationships to pathophysiology of vascular dysfunctions, such as vasospasm and those related to hypertension, diabetes, aging, etc., and the extended roles of NO in nerve function, inflammation, immune reactions, etc. would be clarified more extensively by accelerated progress in this field of research.
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PMID:[Endothelium-derived relaxing factor (EDRF)]. 216 93

Changes in our concepts of angiotensin I converting enzyme are reviewed briefly. The actions of this enzyme go beyond liberating angiotensin II from angiotensin I or inactivating bradykinin. Its very wide distribution in the body and its activity in vitro indicate involvement in the metabolism of other biologically active peptides. The recent molecular cloning of the human enzyme confirmed the existence of a hydrophobic C-terminal peptide that forms the short transmembrane domain of this plasma membrane-bound enzyme. The much longer external portion contains two homologous active site domains but probably only one functional active center. Finally, in spite of the great progress made in studying angiotensin converting enzyme, there are many challenging problems waiting to be solved.
Hypertension 1990 Oct
PMID:Angiotensin I converting enzyme and the changes in our concepts through the years. Lewis K. Dahl memorial lecture. 217 Feb 73

We review below published studies of endothelium-dependent vasodilation in vivo. Endothelium-dependent vasodilation has been demonstrated in conduit arteries in vivo and in the cerebral, coronary, mesenteric, and femoral vascular beds as well as in the microcirculation of the brain and the microcirculation of cremaster muscle. The available evidence, although not complete, strongly suggests that the endothelium-derived relaxing factor generated by acetylcholine in the cerebral microcirculation is a nitrosothiol. The endothelium-derived relaxing factor generated by bradykinin in this vascular bed is an oxygen radical generated in association with enhanced arachidonate metabolism via cyclooxygenase. In the microcirculation of skeletal muscle, on the other hand, the vasodilation from bradykinin is mediated partly by prostacyclin and partly by an endothelium-derived relaxing factor similar to that generated by acetylcholine. Basal secretion of endothelium-derived relaxing factor is controversial in vivo but is usually present in vitro. On the other hand, it appears that endothelium-derived relaxing factor mediates flow-dependent vasodilation in both large vessels and in the microcirculation in vivo. The generation and release of endothelium-derived relaxing factor from endothelium may be abnormal in a variety of conditions including acute and chronic hypertension, atherosclerosis, and ischemia followed by reperfusion. Several mechanisms for these abnormalities have been identified. These include inability to generate endothelium-derived relaxing factor or destruction of endothelium-derived relaxing factor by oxidants after its release in the extracellular space. These abnormalities in endothelium-dependent relaxation may contribute to the vascular abnormalities in these conditions.
Hypertension 1990 Oct
PMID:Endothelium-derived relaxing factors. A perspective from in vivo data. 217 Feb 74

To better understand and treat painful conditions, one needs to identify the cause, discover the source, and develop knowledge of peripheral and central pain transmission; headaches are no exception. The development of appropriate animal models is important. Accordingly, we have reviewed the anatomy, neurochemistry, electrophysiology, and pharmacology of the trigeminovascular system in experimental animals and emphasized whenever possible the relevance of this final common pathway to migraine, cluster, and other headache syndromes in humans. For example, based on recent anatomic dissections, the pericarotid cavernous sinus plexus was suggested as an important focus to investigate cluster headache pathophysiology. This plexus is an anatomic point of convergence for the nerves giving rise to the signs of sympathetic and parasympathetic activity and sensory symptoms that develop in cluster patients. As in other nociceptive systems, trigeminovascular axons assume at least two important roles. One concerns the transmission of nociceptive information. Electrophysiologic evidence supports the trigeminal nucleus caudalis as an important site for the convergence of visceral (vessel) and somatic (forehead) inputs to mediate the referral of vascular pain to superficial tissues. A second important role concerns the initiation of local increases in blood flow and enhanced protein permeability (sterile inflammation) via the axonal release of vasoactive neuropeptides. Plasma extravasation develops within the dura mater following trigeminal stimulation. Extravasation can be blocked by the administration of ergot alkaloids or sumatriptan, a new serotonin-like agonist, and a prejunctional (neuronal) mechanism of action for these drugs (such as blockade of release) was suggested based on experimental evidence. Whether vasoconstriction also relates to the therapeutic efficacy remains to be determined. As in other organ systems, real or threatened tissue injury provides an important stimulus for depolarizing sensory fibers. The stimulus may come from external conditions such as reduced blood flow or hypoglycemia. The brain may also possess intrinsic neuronal mechanisms by which nociceptors may be synthesized (e.g., glutamate-induced neurotoxicity, seizures). Molecules of relevance include bradykinin, prostaglandins, leukotrienes, and potassium. Experimental evidence was presented demonstrating that the trigeminal nerve mediates hyperemia within cortical gray matter by axon-reflex like mechanisms. An important role for this nerve was established during the hyperemic period of recirculation after ischemia or during severe hypertension above the limits of autoregulation.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Basic mechanisms in vascular headache. 217 82

The role of the brain kallikrein-kinin system in the regulation of arterial blood pressure of normotensive and spontaneously hypertensive rats was evaluated. Intracerebroventricular administration of the kinin antagonist [DArg0]Hyp3-Thi5,8[DPhe7]bradykinin caused no change in mean blood pressure in Wistar-Kyoto, Sprague-Dawley, or spontaneously hypertensive rats. The antagonist proved to be very potent in blocking the pressor effect of intracerebroventricular bradykinin (32 +/- 3 vs. 3 +/- 1 mm Hg, p less than 0.01). It was specific, as the pressor effect induced by other unrelated peptides was similar during the infusion of either vehicle or kinin antagonist (angiotensin II, 25 +/- 4 vs. 26 +/- 2 mm Hg; prostaglandin E2, 48 +/- 3 vs. 47 +/- 8 mm Hg; norepinephrine, 17 +/- 2 vs. 18 +/- 2 mm Hg; leucine-enkephaline, 15 +/- 2 vs. 16 +/- 1 mm Hg; neurotensin, 18 +/- 2 vs. 19 +/- 1 mm Hg; substance P, 19 +/- 2 vs. 19 +/- 2 mm Hg). Intracerebroventricular administration of 1 mg captopril, an inhibitor of kininase II (one of the enzymes responsible for kinin degradation), caused no change in mean blood pressure in normotensive rats, whereas it increased mean blood pressure by 44 +/- 9 mm Hg (p less than 0.01) in spontaneously hypertensive rats. This increase in mean blood pressure was blocked and then reversed into a hypotensive effect (22 +/- 6 mm Hg, p less than 0.05) during the infusion of kinin antagonist. Our data suggest that the pressor effect induced by intracerebroventricular captopril is due to a transient elevation in endogenous brain kinin levels, supporting the hypothesis that the brain kallikrein-kinin system plays a role in the central regulation of blood pressure in spontaneously hypertensive rats.
Hypertension 1990 Apr
PMID:Brain kinins are responsible for the pressor effect of intracerebroventricular captopril in spontaneously hypertensive rats. 218 Aug 19


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