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)

The primary mechanism of regulation of smooth muscle contraction involves the phosphorylation of myosin catalyzed by Ca2+/calmodulin-dependent myosin light chain kinase. However, additional mechanisms, both Ca(2+)-dependent and Ca(2+)-independent, can modulate the contractile state of smooth muscle. Protein kinase C was first implicated in the regulation of smooth muscle contraction with the observation that phorbol esters induce slowly developing, sustained contractions. Protein kinase C occurs in at least four Ca(2+)-dependent (alpha, beta I, beta II, and gamma) and four Ca(2+)-independent (delta, epsilon, zeta, and eta) isoenzymes. Only the alpha, beta, epsilon, and zeta isoenzymes have been identified in smooth muscle. Both classes of isoenzymes have been implicated in the regulation of smooth muscle contraction. However, the physiologically important protein substrates of protein kinase C have not yet been identified. Specific isoenzymes may be activated by different contractile agonists, and individual isoenzymes exhibit some degree of substrate specificity. Prolonged activation of protein kinase C can result in its proteolysis to the constitutively active catalytic fragment protein kinase M, which would dissociate from the sarcolemma and phosphorylate proteins such as myosin that are inaccessible to membrane-bound protein kinase C. Protein kinase M induces relaxation of demembranated smooth muscle fibers contracted at submaximal Ca2+ concentrations. We suggest that protein kinase C plays two distinct roles in regulating smooth muscle contractility. Stimuli triggering phosphoinositide turnover or phosphatidylcholine hydrolysis induce translocation of protein kinase C (probably specific isoenzymes) to the sarcolemma, phosphorylation of protein, and a slow contraction. Prolonged association of the kinase with the membrane may lead to proteolysis and release into the cytosol of protein kinase M, resulting in myosin phosphorylation and relaxation.
Hypertension 1992 Nov
PMID:Protein kinase C of smooth muscle. 142 8

The study included 30 patients with borderline essential hypertension (HPT) (21 with a positive family history of hypertension, mean age 24.6 years, 9 with a negative family history, mean age 27.2 years) and 10 normotensive controls (mean age 27.5 years). In all of them 24-hour urinary noradrenaline (NA) and adrenaline (A) excretion was assayed. Blood levels of NA, A and dopamine, the prostacycline metabolite 6-keto-PGF1 alpha, beta-thromboglobulin, cholesterol, triglycerides and HDL cholesterol were measured, LDL cholesterol was calculated according to the Friedewald equation. Besides, lecithin cholesterol acyltransferase activity was assayed. Patients with HPT and a positive family history had elevated sympathetic and platelet activity and diminished 6-keto-PGF1 alpha blood levels. Their HDL cholesterol level was significantly lower than that of healthy controls. In patients with HPT and a positive family history of HPT the atherogenic index (total cholesterol to HDL cholesterol ratio) was highest, but did not differ significantly from that in other groups. The assessment of the examined humoral factors indicates that patients with borderline HPT with genetic predisposition to high blood pressure have a humoral profile different from that of patients without genetic predisposition. These findings suggest the importance of genetic factors in the development of essential HPT.
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PMID:Platelet activity, prostacycline metabolite, plasma lipids and sympathoadrenal activity in patients with borderline hypertension and a positive family history of hypertension. 214 90

The studies involved 22 patients with borderline hypertension and familial history of the arterial blood hypertension (mean age 24.6 years) and 9 patients without familial history of hypertension (mean age 22.2 years). Control group included 10 healthy volunteers (mean age 27.5 years). Erythrocyte Na+ and K+ levels, daily secretion of noradrenaline (NA), adrenaline (A) and dopamine (DA), prostacyclin metabolite 6-keto-PGF1 alpha, beta-thromboglobulin levels (beta-TG), triglyceride cholesterol, and HDL-cholesterol were determined in all examined subjects. Friedewald's equation was used to calculate LDL-cholesterol. Moreover, LCAT activity was measured. An increase in erythrocyte Na+, increased sympathetic activity, excessive platelet activity and decreased 6-keto-PGF1 alpha levels were found in the group of hypertensive patients with familial history of the arterial blood hypertension. HDL-cholesterol was significantly lower in these patients than in the control group. Atherogenic index (cholesterol/HDL-cholesterol ratio) was the highest in the hypertensive patients with familial history of the arterial blood hypertension. The difference was insignificant, however. Patients with the borderline hypertension and familial predisposition to this disease differ from the hypertensive patients without familial history of the arterial hypertension in humoral profile suggesting a contribution of the genetic factors to the development of the arterial blood hypertension.
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PMID:[Intracellular electrolytes and selected biochemical parameters in patients with borderline arterial hypertension and positive family history of hypertension]. 253 29

Subcutaneous injections of elcatonin, a synthetic analogue of eel calcitonin, lowered the blood pressure in DOCA/saline-hypertensive and spontaneously hypertensive rats (SHR), but not in normotensive Wistar rats. The hypotensive effect was more prominent in the DOCA hypertensive rats. Daily injections of elcatonin (10-30 U/kg/day for 21 days) resulted in maximum hypotension on the 4th day in DOCA hypertensive rats and on the 14th day in SHR, and the reduced level of blood pressure was maintained. After the cessation of elcatonin injections, the pressure started to elevate gradually towards the control level. In normotensive rats, elcatonin did not significantly alter the blood pressure for 6 weeks. Daily injections of elcatonin significantly prevented the development of DOCA-induced hypertension and spontaneously-occurring hypertension. Elcatonin-induced hypotension did not differ in the control and parathyroidectomized DOCA hypertensive rats. Elcatonin did not alter the pressor response to noradrenaline, vasopressin and angiotensin II nor the depressor response to isoproterenol, acetylcholine and histamine in DOCA hypertensive rats. It is concluded that the antihypertensive effect of elcatonin is not associated with the release of parathyroid hormone nor with the blockade of alpha, beta, angiotensin II and vasopressin receptors.
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PMID:[Antihypertensive action of elcatonin]. 667 29

Three subunits of the amiloride-sensitive Na+ channel, named alpha, beta, and gamma, have previously been cloned in rat colon. The human lung alpha chain (SCNN1A) has also been cloned and its gene localized on chromosome 12p13. We now report the molecular cloning of the human lung beta (SCNN1B) and gamma (SCNN1G) chains. In situ hybridization and pulsed-field electrophoresis experiments demonstrate that both genes are located within a common 400-kb fragment on chromosome 16p12-p13. Screening of the cDNA library reveals two forms of the beta subunit that differ by the presence or absence of a 464-bp fragment in the 3' region. A frameshift in the short form modifies the COOH terminal sequence of the corresponding protein. Since several similar frameshifts mutations have recently been reported in patients affected by a rare form of hypertension, the existence of COOH truncated forms of the beta chain might be of physiological importance.
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PMID:Cloning, chromosomal localization, and physical linkage of the beta and gamma subunits (SCNN1B and SCNN1G) of the human epithelial amiloride-sensitive sodium channel. 749 94

Proopiomelanocortin (POMC) is a protein that contains the amino acid sequences of numerous peptide hormones, including the melanocyte-stimulating hormones (MSH). MSH peptides of alpha, beta, and gamma primary structure are present in plasma, and all exhibit natriuretic activity. Intravenous infusion of alpha or beta-MSH leads to a time- and dose-dependent natriuresis, whereas gamma-MSH is reported to be natriuretic at low doses but antinatriuretic at high doses. The natriuretic activity of MSH peptides occurs without change in arterial pressure or renal hemodynamics, suggesting a possible direct tubular inhibition of sodium reabsorption. Intravenously infused gamma-MSH is associated with an increase in the plasma concentration of atrial natriuretic peptide. In addition, gamma-MSH also has a direct intrarenal natriuretic action that is dependent on the renal nerves. In rats, gamma-MSH-related peptides are involved in the reflex control of sodium excretion in situations such as the natriuresis that occurs (a) from the remaining kidney after acute unilateral nephrectomy, (b) from the contralateral kidney shortly after unilateral ureteral pressure elevation, and (c) after unilateral carotid artery traction. POMC-derived peptides (including MSH) are modulated in response to salt loading, and alterations in POMC metabolism and plasma peptide concentrations have been observed in genetically hypertensive rats and during the development of adrenal regeneration hypertension. In addition, plasma gamma-MSH levels are elevated in patients with severe congestive heart failure, and in primary hyperaldosteronism. These observations suggest a possible involvement of MSH-related peptides in sodium homeostasis as well as in certain forms of hypertension.
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PMID:Natriuretic properties of melanocyte-stimulating hormones. 750 15

Adenosine triphosphate (ATP), a co-transmitter in sympathetic nerves and released from platelets, has recently been shown to stimulate growth of vascular smooth muscle cells. It might therefore contribute to the development of vascular hypertrophy seen in hypertension and atherosclerosis. We aimed at characterising the receptor mediating this mitogenic effect in rat aorta smooth muscle cells. The potency of agonists indicates a P2 purinoceptor since ATP > or = ADP >> AMP, adenosine. The P2x-receptor subtype, which is responsible for ATP induced vasoconstriction in rat aorta, does not mediate the mitogenic effect since alpha, beta-methyleneATP had no effect and beta, gamma-methyleneATP had lower potency than ATP. The P2Y-receptor subtype was excluded since the selective agonist 2-methylthioATP had weak effect with lower potency than ATP. When we studied the involvement of other nucleotides similar effects were seen of the purines ATP, GTP and ITP; also the pyrimidine UTP had powerful mitogenic effects (Emax = 52% of ATP) with similar potency. Nucleotides with fewer phosphate groups showed a stepwise fall in mitogenic effect. This indicates involvement of a nucleotide-receptor (P2U). Ap4A were of equal potency and effect as ATP. There was strong correlation between the mitogenic effects of the nucleotides and analogues with both 45Ca(2+)-influx and inositol phosphate (IP) production, indicating that they may participate in mediating the mitogenic response. This is the first study describing the potencies for the mitogenic effects of the selective ATP-analogues and other nucleotides in vascular smooth muscle cells. The receptor characterisation indicates a nucleotide-receptor similar to the receptor which stimulates 45Ca(2+)-influx and inositol phosphate-formation in rat aorta smooth muscle cells. Substances related to ATP such as GTP, ITP, UTP and Ap4A which also can be released extracellularly in vivo stimulate mitogenesis of rat aorta smooth muscle cells through the same receptor.
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PMID:Characterisation of an ATP receptor mediating mitogenesis in vascular smooth muscle cells. 778 5

The tests have been carried out on 64 women in 3rd trimester of pregnancy. 30 of them were the women with a normal course of pregnancy, and 34 were the ones with hypertension induced pregnancy (PIH). Their blood serum has been tested for the concentration of TG, phospholipids, total cholesterol, HDL- and LDL-cholesterol, alpha, beta and pre-beta lipoprotein fractions. The results have been calculated statistically. It has been found that the increase in the concentration of TG (p < 0.001), phospholipids (p < 0.02), total cholesterol (p < 0.01), the beta lipoprotein fraction (p < 0.001) was essentially higher in the women with PIH, in 3rd trimester of pregnancy, in comparison to those values observed in the healthy pregnant women. At the same time a lower concentration of alpha lipoproteins (p < 0.01) has been observed in the group of the pregnant with pregnancy induced hypertension.
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PMID:[Concentration of lipids and lipoproteins in serum of women with pregnancy induced hypertension]. 857 78

Liddle syndrome is an autosomal dominant form of hypertension, resulting from mutations in the cytoplasmic C-terminus of either the beta or gamma subunits of the amiloride-sensitive epithelial Na channel (ENaC) which lead to constitutively increased channel activity. Most mutations reported to date result in the elimination of 45-75 normal amino acids from these segments, leaving open the question of the identity of the precise amino acids in which mutation can lead to an enhanced channel activity. To address this question, we have performed a systematic mutagenesis study of the C-termini of the alpha, beta and gamma ENaC subunits of the rat channel and have analyzed their function by expression in Xenopus oocytes. The results demonstrate that a short proline-rich segment present in the cytoplasmic C-terminus of each subunit is required for the normal regulation of channel activity. Missense mutations altering a consensus PPPXY sequence of the alpha, beta or gamma subunits reproduced the increase in channel activity found in mutants in which the entire cytoplasmic C-termini are deleted. This proline-rich sequence, referred to as the PY motif, is known to be a site of binding by proteins bearing a WW domain. These findings show that the three PY motifs in the C-termini of ENaC are involved in the regulation of channel activity, probably via protein-protein interactions. This new regulatory mechanism of channel function is critical for the maintenance of normal Na reabsorption in the kidney and of Na+ balance and blood pressure.
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PMID:Identification of a PY motif in the epithelial Na channel subunits as a target sequence for mutations causing channel activation found in Liddle syndrome. 866 45

The pituitary prohormone proopiomelanocortin gives rise to melanocortins of alpha, beta, and gamma primary structure in addition to corticotropin. Melanocortins have a variety of actions in mammals, and each is natriuretic. In particular, gamma-melanocyte-stimulating hormone has been shown to mediate reflex natriuresis after acute unilateral nephrectomy. We examined whether this peptide could play a role in longer term adjustments in sodium balance by measuring plasma gamma-melanocyte-stimulating hormone and corticotropin concentrations, as well as pituitary proopiomelanocortin mRNA abundance, in Sprague-Dawley rats ingesting either a low (0.07% NaCl) or high (7.5% NaCl) sodium diet. One week after the high sodium diet, plasma gamma-melanocyte-stimulating hormone concentration was double the value seen in rats on the low sodium diet (158 +/- 5 [SE] versus 76 +/- 9 fmol/mL, P < .001), a change that was accompanied by a fivefold increase in plasma atrial natriuretic peptide concentration but no change in plasma corticotropin. Whole pituitary proopiomelanocortin mRNA abundance, measured with a probe to exon 3 of the rat proopiomelanocortin gene, was significantly increased after 1 week of the high sodium diet compared with the low sodium diet and increased further at 2 and 3 weeks. This increase occurred primarily in the neurointermediate lobe as demonstrated by in situ hybridization; the content of gamma-melanocyte-stimulating hormone immunoreactivity was also increased in this lobe, but not the anterior lobe, after 1 week of the high sodium diet. These results demonstrate that high dietary sodium intake increases neurointermediate lobe proopiomelanocortin mRNA abundance compared with a very low sodium diet and also suggest that proopiomelanocortin is preferentially processed into gamma-melanocyte-stimulating hormone rather than corticotropin. These observations consequently raise the possibility of a role for this peptide hormone system in the adjustments to a high salt diet.
Hypertension 1996 Aug
PMID:Dietary sodium intake modulates pituitary proopiomelanocortin mRNA abundance. 870 89


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