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

The response of isolated blood vessels to a variety of vasoactive agonists is modulated by the presence of endothelial cells. Indeed, these cells can release both dilator and constrictor substances. The major endothelium-derived relaxing factor may be nitric oxide, which activates soluble guanylate cyclase in the smooth muscle, although the endothelial cells also secrete an unidentified hyperpolarizing factor. Among the natural stimuli for the release of endothelium-derived relaxing factors are circulating hormones, platelet products, thrombin, shear stress, and certain autacoids. Endothelium-derived relaxing factors may contribute to the regulation of the release of atrial natriuretic factor and renin. The endothelial cells can also release constricting factors; among the likely candidates are superoxide anions or the peptide endothelin. In hypertensive blood vessels, the ability to release endothelium-derived relaxing factors but not endothelium-derived contracting factors is blunted.
Hypertension 1989 Jun
PMID:Endothelium and control of vascular function. State of the Art lecture. 266 25

1. We have examined the effects of a range of smooth muscle relaxants on the maintained contractions produced in rat aortic rings by the protein kinase C activator, 4 beta-phorbol dibutyrate; these effects were compared with those on the contraction induced by the selective alpha 1-adrenoceptor agonist, methoxamine. The phorbol ester, at 0.3 microM, gave a sustained contraction which was, on average, of approximately the same magnitude as the maximum contraction produced by methoxamine, 10 microM. 2. The beta-adrenoceptor agonist, isoprenaline (0.01-1 microM) caused a dose-related relaxation of the methoxamine-induced contraction but had no effect on the contraction induced by the phorbol ester. 3. An activator of adenylate cyclase, forskolin (0.01-1 microM) produced a dose-related relaxation of the methoxamine-induced contraction and at 0.01-10 microM caused relaxation of the contraction induced by the phorbol ester. Similar results were obtained with the potassium channel activator, cromakalim (0.001-10 microM). 4. An activator of guanylate cyclase, sodium nitroprusside (0.001-100 microM) caused a dose-related relaxation of both the methoxamine-induced and the phorbol ester-induced contraction, being more effective on the former than on the latter. Similar results were obtained with enprofylline (1-1000 microM). 5. Methoxamine (10 nM-100 microM), given cumulatively, caused a dose-related contractile response. Pretreatment with isoprenaline (1 microM), enprofylline (10 microM) and nicorandil (1 microM) resulted in partial decrease of the subsequent response to methoxamine, while nicorandil (10 microM), forskolin (1 microM), sodium nitroprusside (10 microM) and cromakalim (1 microM) totally abolished it. 6. The phorbol ester, given cumulatively, caused increasing contraction in the concentration range 30 nM-10 microM. Pretreatment with forskolin (1 microM), sodium nitroprusside (10 microM), isoprenaline (1 microM), enprofylline (10 microM), nicorandil (1 microM or 10 microM), or cromakalin (1 microM or 10 microM), resulted in partial decrease of the subsequent response to 4 beta-phorbol dibutyrate. 7. These results are discussed in the light of the suggestion that protein kinase C may have a role in the 'latch-bridge' phase of smooth muscle contraction, and that inappropriate activation of protein kinase C may contribute to the pathogenesis of hypertension and other conditions involving vasospasm.
 ...
PMID:The effect of relaxants working through different transduction mechanisms on the tonic contraction produced in rat aorta by 4 beta-phorbol dibutyrate. 275 36

The sequence of atrial natriuretic factor (ANF) has been determined, as well as the complete structure of the rat and human complementary DNA and gene. ANF and ANF messenger RNA are present not only in atria but also in ventricles. The circulating form of ANF has been identified as the C-terminal of the molecule, ANF (Ser 99-Tyr 126). The isolated secretory granules of rat atrial cardiocytes contain only pro-ANF (Asn 1-Tyr 126). An enzyme (IRCM-SP1) has been isolated from heart atria and ventricles. This enzyme is highly specific in cleaving ANF (Asn 1-Tyr 126), to yield ANF (103-126), (102-126), and (99-126). In target cells, ANF produces a rise in cyclic guanosine 3',5'-monophosphate (cGMP) due to activation of particulate guanylate cyclase, and inhibition of adenylate cyclase leading in some cases to a decrease in cyclic adenosine 3',5'-monophosphate (cAMP). ANF produces relaxation of rabbit and rat aortic strips, inhibits steroidogenesis in both zona glomerulosa and zona fasciculata cells, and inhibits the release of arginine vasopressin from the isolated rat hypothalamohypophysial preparation in vitro but decreases AVP release in vivo only at pharmacological doses. In all forms of experimental hypertension, plasma levels of ANF are increased and, at some time periods, atrial levels are also decreased. The ventricular levels of immunoreactive ANF are also increased in renal hypertension. Infusion of ANF by minipumps decreases the blood pressure near control levels in several models of experimental hypertension. In cardiomyopathic hamsters with heart failure, the atrial levels of immunoreactive ANF are decreased while the plasma and ventricular levels are increased.(ABSTRACT TRUNCATED AT 250 WORDS)
Hypertension 1987 Nov
PMID:The heart as an endocrine gland. 282 60

The cellular mechanism of the action of atrial natriuretic factor (ANF) is thought to involve activation of guanylate cyclase. Increasing evidence shows a direct tubular effect of ANF. Part of the ANF-induced diuresis has been suggested to be due to inhibition of the action of arginine vasopressin (AVP) in the cortical collecting tubule. In this study we investigated the effect of ANF on cyclic nucleotide production in primary cultures of cortical collecting tubule cells immunodissected with a monoclonal antibody. ANF caused a dose-dependent stimulation in cyclic guanosine 3',5'-monophosphate (cGMP) production; the half-maximal stimulation was observed at approximately 1 nM of ANF. ANF (0.01-100 nM) had no effect on cyclic adenosine 3',5'-monophosphate (cAMP) accumulation in cortical collecting tubule cultures. AVP caused a dose-dependent increase in cAMP production, and this effect was not altered by the simultaneous addition of ANF (100 nM). Similarly, ANF-induced cGMP stimulation was not influenced by AVP (10 nM). We conclude that 1) ANF has a direct stimulatory action on cGMP production by cultured cortical collecting tubule cells and 2) any interaction between ANF and AVP is likely to occur at steps distal to cyclic nucleotide formation.
Hypertension 1988 Apr
PMID:Effects of atrial natriuretic factor and vasopressin on cyclic nucleotides in cultured kidney cells. 283 39

Abnormalities in the coupling of atrial natriuretic factor (ANF) receptors with the guanosine 5'-cyclic monophosphate (cGMP) system in vascular smooth muscle cells (VSMCs) may play a role in the pathophysiology of hypertension in the spontaneously hypertensive rat (SHR). This concept was examined in cultured, aortic VSMCs (passages 6-10) from SHR, Wistar-Kyoto (WKY), and American Wistar (Wis) rats. Quiescent VSMCs of the SHR (serum deprived for 24 h) had higher ANF receptor density (Bmax) and lower affinity [i.e., increased equilibrium dissociation constant (Kd)] than cells from normotensive controls. Maximal binding (Bmax) (specific binding sites/cell) values for these cells were SHR 112,855 +/- 6,951, WKY 48,650 +/- 3,607, and Wis 36,122 +/- 2,607 (means +/- SE; P less than 0.001 for SHR vs. both WKY and Wis). The Kd values were (in nM) SHR 1.20 +/- 0.098, WKY 0.657 +/- 0.065, and Wis 0.37 +/- 0.037 (P less than 0.001 for SHR vs. both WKY and Wis). Despite their higher Bmax, VSMCs of the SHR showed a substantially lower maximal stimulation of cGMP accumulation in response to ANF: 987 +/- 29.3, 1,992 +/- 574.2, and 2,019 +/- 273.8 fmol.4 min-1.10(6) cells-1 for SHR, WKY, and Wis, respectively (P less than 0.01 for SHR vs. Wis and P less than 0.02 for SHR vs. WKY). Further experiments demonstrated that the poor response of SHR VSMCs to the ANF was not due to a population of receptors that did not couple to the particulate guanylate cyclase. Such findings demonstrate a dissociation of the cGMP response to ANF from the binding of the hormone to its receptors in VSMCs of the SHR compared with controls. This appears to represent a primary and innate defect in these cells that may contribute to the hypertensive process in the SHR.
 ...
PMID:Blunted cGMP response to ANF in vascular smooth muscle cells of SHR. 284 33

Both our previous and the present studies established that increases in cyclic guanosine monophosphate (cGMP) reflect the activity of atrial natriuretic factor (ANF). The ANF message is transmitted by particulate guanylate cyclase, which appears to be in intimate contact with the ANF receptor since stimulation of particulate guanylate cyclase is observed even after dispersion of the membranes. The stimulation of smooth muscle and endothelial cells in culture leads to egression of cGMP to extracellular medium where it accumulates for over 2 h. The signal of the extracellular cGMP is magnified and prolonged compared to the intracellular signal. The stimulation of cGMP production by ANF in vascular smooth muscle and endothelial cells appears to be relatively irreversible and the responsiveness is down-regulated by prior exposure to low doses of ANF. Cyclic guanosine monophosphate can also serve as a marker for ANF action. Atrial natriuretic factor fragments of different potencies exert a biological activity that correlates with ANF-induced cGMP increases. In hypertensive rats and monkeys, where acute infusion of ANF leads to an exaggerated diuresis and natriuresis, urinary cGMP does not appear to be different. Overall, cGMP appears to be a mediator and a marker of ANF biological activity and may serve as a useful tool in the study of pathogenesis of hypertension.
 ...
PMID:Cyclic GMP as mediator and biological marker of atrial natriuretic factor. 287 13

Drugs that inhibit endothelium-dependent relaxation were tested to determine their effect on soluble guanylate cyclase purified from dog aorta. Basal, arachidonic acid (10(-5) M)-stimulated, and nitroprusside (5 X 10(-5) M)-stimulated guanylate cyclase activities were inhibited by methylene blue and the lipoxygenase inhibitors nordihydroguaiaretic acid and eicosatetraynoic acid. The effective inhibitory doses were in the range of those that have been reported to inhibit endothelium-dependent relaxation. Other compounds known to inhibit endothelium-dependent relaxation had little or no effect on guanylate cyclase activity. Basal guanylate cyclase activity was more resistant to inhibition than were activated states of the enzyme. The data suggest that reported inhibition of endothelium-dependent relaxation by some lipoxygenase inhibitors may be the result, at least in part, of their direct effect on guanylate cyclase activity.
Hypertension 1986 Oct
PMID:Modulation of guanylate cyclase by lipoxygenase inhibitors. 287 47

As hypertension developed in spontaneously hypertensive rats (SHR), the plasma concentration of atrial natriuretic factor (ANF) increased whereas its tissue concentration in the atria decreased. These observations suggest that ANF is secreted from the atria in response to hypertension. Atrial natriuretic factor contents in the hypothalamus and pons decreased with ageing in Wistar-Kyoto rats (WKY) but not in SHR. The responses of various SHR tissues to the hypotensive, vasorelaxant and cyclic GMP generating effects of ANF were more pronounced than in corresponding WKY tissues. The number of ANF receptors was reduced without change in the affinity in aortic smooth muscle and adrenals of SHR with established hypertension. These findings suggest that the elevated sensitivity to ANF of blood pressure of SHR can be in part explained by the increased sensitivity to ANF of guanylate cyclase in the vascular wall of SHR.
 ...
PMID:Atrial natriuretic factor in spontaneously hypertensive rats: concentration changes with the progression of hypertension and elevated formation of cyclic GMP. 287 70

A short and up-to-date review on the great advances made in the field of the atrial natriuretic factor (ANF) is presented. All the short active peptides (up to 33 AA) isolated after purification of atrial homogenates have the same core of 23 amino acids (Ser 103-ARG 125). The ANF liberated in the medium of cultures of rat atrial cardiocytes is the 26 amino acid Arg 101-Tyr 126. Cloning of the cDNA encoding for ANF and of the rat, mouse, and human ANF gene has been accomplished. ANF has a most potent and short-lasting diuretic and natriuretic effect that appears to be predominantly due to a significant increase in glomerular filtration rate. ANF inhibits the release of aldosterone both in vitro and in vivo. It produces a profound inhibition of vascular contraction induced by norepinephrine and angiotensin II. This vasorelaxation is followed by a prolonged refractory period. ANF administration corrects the hypertension in 2K-1C hypertensive rats and in spontaneously hypertensive rats. Specific high-density binding sites have been found in the brain, especially in the hypothalamus, subfornical organ, median eminence, area postrema, and nucleus tractus solitarius, all areas involved in the brain control of hypertension and in the regulation of salt and water. ANF has no effect on the known sodium transport mechanisms across cell membrane. It has a major effect on the stimulation of guanylate cyclase activity, especially in renal glomeruli. Specific radioimmunoassay procedures have been established and results of preliminary studies that establish clearly that ANF is a circulating hormone are presented.
 ...
PMID:Atrial natriuretic factor. 294 45

Apart from the generally known functions, the heart has also an endocrine function. Atrial cardiocytes, being typical secretory cells, release peptide hormones into the blood stream: atrial natriuretic peptide containing 28 amino acids and cardiodilatin. The structure of atrial peptides was determined. It was shown that both peptides were derived from their common precursor, a protein containing 151 amino acids. The presence of specific receptors is demonstrated on plasmatic membranes of cells of kidney epithelium, arterial smooth muscle, arterial endothelium, kidney cortex and hypophysis. The interaction of atrial peptides with these receptors activates the guanylate cyclase system. The biological action of atrial peptides manifests itself in the quick, massive and instantaneous increase of diuresis and electrolyte excretion, elevated clearance of creatinine, decrease of kidney vascular resistance, intensification of glomerular filtration, inhibition of stimulated secretion of aldosterone, relaxation of blood vessels, elimination of arterial and intestinal spasm induced by various endogenous and exogenous vasoconstrictors and in correction of kidney hypertension. Various radioimmunoassays for the presence of atrial peptides in human plasma were developed; it was shown that in patients with congestive heart failure the content of atrial peptides is increased.
 ...
PMID:[Endocrine function of the heart. Structure and biological properties of peptides secreted by the heart atrium]. 295 15


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>