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

1. Dibutyryl cyclic AMP (Db cAMP, 75-500 microgram/kg), injected into the lateral ventricle of the brain of the cat increased blood pressure, heart rate and splanchnic discharge rate. 2. ATP, but not AMP, induced similar changes; GMP in small doses increased blood pressure. 3. A number of drugs are known to activate adenylate cyclase-induced hypertension, tachycardia and increase splanchnic discharge rate. This was shown for TRH, tetracosactide and a new beta2-adrenoceptor stimulant, NAB 365. 4. Injection into the lateral ventricle of theophylline or Ro 7/2956, both inhibitors of phosphodiesterase, similarly increased blood pressure. 5. Histamine administered by the same route induced similar reactions; it is not known if this action was exerted by activation of H1- or H2-receptors. 6. Somatostatin, known to reduce cAMP levels, induced a small but significant decrease in blood pressure. Melanocyte stimulating hormone release inhibiting factor (MIF) and TSH were ineffective. 7. These results provide evidence for the possibility of a role for cAMP in the central regulation of blood pressure at suprabulbar levels.
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PMID:Cyclic 3'5'-adenosine monophosphate and central circulatory control in cats and dogs. 2 Feb 56

Endothelium-dependent relaxation of carotid arteries and changes in levels of cyclic (c)GMP between stroke-prone spontaneously hypertensive (SHRSP) and Wistar-Kyoto (WKY) rats have been compared. The concentration-response curve for acetylcholine (ACh)-induced relaxation was shifted to the right in carotid arteries from SHRSP. Relaxation responses produced by calcimycin (A 23187) and melittin, both endothelium-dependent agents, were depressed in carotid arteries from SHRSP. Relaxation responses produced by sodium nitroprusside and 8-Br-cGMP were similar to those in strips from WKY. ACh-induced production of cGMP was significantly decreased in carotid arteries from SHRSP when compared with the level for similarly treated strips from WKY. These results suggest that functional changes in endothelium, but not guanylate cyclase activity or cGMP sensitivity in the carotid arteries, may occur in hypertension. Thus, impaired endothelium-dependent relaxation in SHRSP may play an important role in hypertensive vascular diseases such as stroke.
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PMID:Impairment of endothelium-dependent relaxation and changes in levels of cyclic GMP in carotid arteries from stroke-prone spontaneously hypertensive rats. 198 99

c-AMP, c-GMP, HVA and 5 HIAA cerebrospinal fluid levels were investigated in 18 patients with subarachnoid haemorrhage (SAH). The main findings in the acute stage after SAH were represented by a marked increase of c-AMP and 5 HIAA values, whereas HVA levels were only slightly higher. In the chronic phase c-GMP levels turned out to be significantly increased, and were clearly related to intracranial hypertension. 5 HIAA and particularly HVA levels were decreased, probably due to the functional and anatomical lesion of the periventricular adrenergic structures, following the raised intracranial pressure.
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PMID:Cerebrospinal fluid levels of cyclic nucleotides and monoaminergic metabolites in subarachnoid haemorrhage: preliminary report. 616 98

Effects of dietary Streptococcus faecalis (SF) on aging were evaluated using 1-week, 6-month, and 27-month-old Wistar and SHR rats. SF was lyophilized and added to commercial pellets at 1%. SF inhibited hypertension in aging SHR. SF inhibited aging-related changes in a wide variety of tissues. These changes were a disarray of hepatic cords, portal fibrosis; calcification of cartilage matrix, dominance of chondroitin sulfate B, and keratosulfate over chondroitin sulfates A and C; aortic endothelial damage, segmental thickening, calcification, and chondroid cells in the intima; atrophy of epidermis and appendages, and increase in amorphous dermal matrix; waxy degeneration and atrophy of psoas muscles; increase in lipoperoxides in the serum, liver, and brain; and reduction of cyclic AMP and GMP in the serum. Histological changes of the xyphoid cartilage, aorta, mesenteric artery, liver, dorsal skin, and psoas muscles in 27-month-old SF rats were much less severe than those in controls.
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PMID:Inhibition of aging changes by lyophilized Streptococcus faecalis in diet. 640 63

From Oct. 1990 to June 1991, alpha-granule membrane protein (GMP 140) were measured by MoAb radioimmunoassay in normal non-pregnant women (n = 24), normal late pregnancy (n = 26), late pregnancy with pregnancy-induced hypertension (PIH) (n = 27), and oral contraceptive users (n = 23). The results showed that (1) platelet GMP 140 of late pregnant women were significantly higher than that in nonpregnant controls; (2) There was no difference in GMP 140 between late pregnant group and PIH group; (3) Differences were not found among mild, moderate and severe PIH subgroups; (4) Platelet GMP140 was remarkably higher in oral contraceptive users than that in normal controls.
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PMID:[Determination of platelet alpha-granule membrane protein in late pregnancy and oral contraceptive users]. 768 74

The amount of, and response of the kidneys to, endogenous natriuretic factor(s) could be important in the pathogenesis of essential hypertension. Searching for possible disturbance(s) related to atrial natriuretic factor (ANF) and its second messenger, cyclic guanosine monophosphate (c-GMP), we assessed plasma immunoreactive (ir) ANF and c-GMP, effective renal plasma flow (ERPF), glomerular filtration rate (GFR), urinary c-GMP, absolute and fractional (FE) excretions of sodium (Na) and chloride (Cl) before and during infusions of low ANF doses or vehicle (V) in 7 normotensive sons of essential hypertensive parents (SEH) compared with 7 sons of normotensive parents (SN). Each subject was infused at 2-week intervals in a single-blind randomized sequence with 4 different solutions: V only or ANF 0.004, 0.008 and 0.016 microgram/kg/min, infused over 90 min. Plasma irANF was lower in SEH than in SN (p < 0.001) during vehicle infusion. Basal plasma c-GMP levels were, on all 4 different study days lower (p < 0.05 to < 0.01) in SEH in SN. Response of plasma c-GMP to infused ANF was also slightly decreased in SEH (p < 0.05 to < 0.01). BP, ERPF and GFR did not differ between SEH and SN and were unchanged during the 4 infusions. Urinary c-GMP excretion, FENa and FECl increased dose-dependently during ANF (p < 0.05 to < 0.0001) but not V infusions. These findings indicate that at the stage of pre-hypertension a disturbance in the ANF-c-GMP regulatory pathway may occur, which is expressed primarily at the circulatory rather than the renal excretory level.
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PMID:Reduced plasma cyclic GMP but normal renal responses to atrial natriuretic factor in pre-hypertension. 877 68

The arterial wall is structurally and functionally compartmentalized. Each compartment is characterized by a specific cell type and by specific interactions. The endothelial compartment interacts with circulating blood, and the adventitial compartment with the surrounding tissue. The media, which contains the effector smooth muscle cells, perceives centrifugal messages from the endothelium and centripetal messages from metabolically active tissues, from adventitial nerve endings, and from peptides produced in the interstitium. The degree of contraction or relaxation of the vascular smooth muscle cells characterizes the general vasomotor tone, which governs the local blood pressure level and distributes the flow according to metabolic needs. The main physiologic vasoactive agent is nitric oxide (NO) and is produced by the endothelium. In disease states, other agents can become predominant in centrifugal parietal messages. NO is produced by type 3 NO synthase, an enzyme that is constitutively expressed by endothelial cells. The activity of this enzyme on its substrate, arginine, is regulated by the concentration of free calcium and by intracellular phosphorylations. Several peptides, including receptors, are coupled to the phospholipase C pathway in the endothelial cell; endothelial growth factors such as FGF and VEGF, enhance the activity of endothelial NO synthase. However, the main physiologic factor responsible for endothelial NO synthase activation is the shearing stress produced by friction of the flowing blood against the immobile vessel wall. This shearing stress constantly adjusts the diameter of conductance vessels to peripheral metabolic needs. Expression of endothelial NO synthase is modulated by the chronic effects of the same agents. NO has a vasodilating effect that is mediated by the generation of cyclic GMP. Cyclic GMP and cyclic AMP are the main second messengers in smooth muscle cell relaxation. NO binds to a heme-protein, soluble guanylate cyclase, that converts GMP to cyclic GMP. Kinase-G is the main target for cyclic GMP in the smooth muscle cell. Kinase-G phosphorylates phospholambans and releases the repumping activity of calcium ATPase. More importantly, kinase-G phosphorylates the protein G that links seven-domain membrane-spanning receptors to phospholipases, thus inhibiting coupling between the ligand-receptors interaction and the intracellular signaling process that leads to contraction. NO can relax the smooth muscle cell only in the presence of a preexisting contractile tone. Conversely, absence of NO enhances the preexisting contractile tone. All these notions can be analyzed via the experimental model of L-NAME-induced chronic NO synthase blockade in rats. The decrease in parietal cyclic GMP seen in this model is associated with an increase in contractile tone that translates into systemic arterial hypertension. The increase in contractile tone can be blocked by renin-angiotensin system inhibitors. Chronic blockade of NO production rapidly induces vascular wall phenotype changes that lead to renal failure, ischemic stroke, and fibrosis of target organs. These phenotype changes may be related to the increase in the oxidative potential of the various types of parietal cells, as suggested by the abnormal presence of inflammatory cells and by the increased expression of inflammation mediators including cyclooxygenase II, inducible NO synthase, and adhesion molecules such as ICAM and VCAM. This model therefore holds promise for elucidating interactions between NO and arteriosclerosis. NO system dysfunction is also seen in other cardiovascular disorders, including congestive heart failure.
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PMID:[Role of endothelial nitric oxide in the regulation of the vasomotor system]. 976 14

Increased parity is more common in lower-socioeconomic groups. Additionally, GMPs tend to be older. It is for these reasons that there is a tendency for an increased incidence of antenatal complications, such as hypertension and diabetes, among GMP mothers. It appears that the previous conflicting reports on the effect of high parity on perinatal outcome can be related to differences in the socioeconomic conditions of the parturient population under examination. Previous evidence of the unfavorable influence on perinatal outcome of high parity might have been biased by patient selection, because high parity is often inversely linked to social class. Our recent studies of the Israeli maternal population plus comparable reports from other countries allow us to conclude that GMP is not always a great cause for concern in an economically stable and healthy population that has access to high-quality medical care. As such, the term dangerous multipara should be removed from the medical literature and the focus of concern should shift to the organization and the delivery of quality medical services.
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PMID:Grandmultiparity. Is it a perinatal risk? 977 32

The objectives of the present study were (1) to determine whether oxidized LDL and lysophosphatidylcholine (lyso-PtdCho), a major phospholipid component of oxidized LDL, stimulate the migration of cultured human mesangial cells and (2) to investigate the possible effects on mesangial cell migration of the cardiac natriuretic peptides atrial and brain natriuretic peptide (ANP and BNP). Oxidized LDL (10 and 100 microg/mL) and lyso-PtdCho (10(-7) to 10(-5) mol/L) stimulated migration in a concentration-dependent manner. In contrast, the effects of native LDL and phosphatidylcholine were modest or nonexistent. Protein kinase C (PKC) inhibitor and downregulation of PKC activity by phorbol ester inhibited oxidized LDL- and lyso-PtdCho-induced migration. Human ANP(1-28) and human BNP-32 significantly inhibited oxidized LDL- and lyso-PtdCho-induced migration in a concentration-dependent manner. C-ANF (des-[Glu(18),Ser(19),Gly(20),Leu(21),Gly(22)]ANP(4-23)), a specific ligand for ANP clearance receptors, could not inhibit oxidized LDL- and lyso-PtdCho-induced migration. Inhibition by ANP and BNP of lyso-PtdCho-induced migration was paralleled by an increase in the cellular level of GMP. Oxidized LDL- and lyso-PtdCho-induced migrations were inhibited by 8-bromo-cGMP. The results suggest that oxidized LDL and lyso-PtdCho stimulate the migration of human mesangial cells, at least in part, through a PKC-dependent process and that ANP and BNP inhibit this stimulated migration, probably through a cGMP-dependent process.
Hypertension 2000 Apr
PMID:Effects of cardiac natriuretic peptides on oxidized low-density lipoprotein- and lysophosphatidylcholine-induced human mesangial cell migration. 1077 71

The prognosis of patients with pulmonary arterial hypertension (PAH) is poor. Available therapies (Ca(++)-channel blockers, epoprostenol, bosentan) have limited efficacy or are expensive and associated with significant complications. PAH is characterized by vasoconstriction, thrombosis in-situ and vascular remodeling. Endothelial-derived nitric oxide (NO) activity is decreased, promoting vasoconstriction and thrombosis. Voltage-gated K+ channels (Kv) are downregulated, causing depolarization, Ca(++)-overload and PA smooth muscle cell (PASMC) contraction and proliferation. Augmenting the NO and Kv pathways should cause pulmonary vasodilatation and regression of PA remodeling. Several inexpensive oral treatments may be able to enhance the NO axis and/or K+ channel expression/function and selectively decrease pulmonary vascular resistance (PVR). Oral L-Arginine, NOS' substrate, improves NO synthesis and functional capacity in humans with PAH. Most of NO's effects are mediated by cyclic guanosine-monophosphate (c-GMP). cGMP causes vasodilatation by activating K+ channels and lowering cytosolic Ca++. Sildenafil elevates c-GMP levels by inhibiting type-5 phosphodiesterase, thereby opening BK(Ca). channels and relaxing PAs. In PAH, sildenafil (50 mg-po) is as effective and selective a pulmonary vasodilator as inhaled NO. These benefits persist after months of therapy leading to improved functional capacity. 3) Oral Dichloroacetate (DCA), a metabolic modulator, increases expression/function of Kv2.1 channels and decreases remodeling and PVR in rats with chronic-hypoxic pulmonary hypertension, partially via a tyrosine-kinase-dependent mechanism. These drugs appear safe in humans and may be useful PAH therapies, alone or in combination.
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PMID:The NO - K+ channel axis in pulmonary arterial hypertension. Activation by experimental oral therapies. 1471 30


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