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)

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

Besides generally known functions, the heart has also an endocrine function. Atrial cardiocytes, being typical secretory cells, released peptide hormones into the blood stream: atrial natriuretic peptide containing 28 amino acids and cardiodiolatin. The structure of atrial peptides was determined. It was shown that both derived from their common precursor, a protein containing 151 amino acid. The presence of specific receptors was 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 activated the guanylate cyclase system. The biological action of atrial peptides manifested itself in the quick, massive and instantaneous increase of diuresis and electrolyte excretion, elevation of 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 correction of kidney hypertension. Various radioimmunoassays for detection of atrial peptides in human blood plasma were developed; it was shown that in patients with congestive failure the atrial peptide content was increased.
 ...
PMID:[A new approach to the problem of cardio-vascular regulation: the endocrine function of the heart (review of the literature)]. 295 52

The biochemical mechanism of action of synthetic atrial natriuretic factor (atriopeptin II) was studied in vascular smooth muscle of the rabbit thoracic aorta. Atriopeptin II caused a time-dependent and concentration-dependent increase in tissue levels of cyclic guanosine monophosphate that corresponded in these same tissues with vascular relaxation. The elevation of arterial cyclic guanosine monophosphate levels preceded the onset of vascular relaxation. Atriopeptin II did not alter vascular levels of cyclic adenosine monophosphate. The presence of a functionally intact vascular endothelium was not necessary for atriopeptin II to elicit vascular relaxation. Atriopeptin II-induced vascular relaxation and elevation of cyclic guanosine monophosphate levels were inhibited by the guanylate cyclase inhibitor methylene blue. These data suggest cyclic guanosine monophosphate mediates vascular relaxation produced by atriopeptin II.
Hypertension
PMID:Cyclic guanosine monophosphate mediates vascular relaxation induced by atrial natriuretic factor. 298 20

A large number and variety of compounds (acetylcholine, adenosine diphosphate, adenosine triphosphate, arachidonic acid, bradykinin, Ca2+ ionophores, calcitonin gene-related peptide, histamine, hydralazine, substance P, thrombin, and vasoactive intestinal polypeptide) have been shown to relax arterial smooth muscle indirectly. The endothelium in muscular arteries from several species appears to have receptors for these vasodilators. Binding of one of these compounds to its endothelial receptors results in the release (and presumably synthesis) of substance(s) that act on arterial smooth muscle to cause relaxation. The name endothelium-derived relaxing factor (EDRF) has been proposed for the substance or substances responsible for inhibition of contraction. Studies to determine additivity of endothelium-dependent relaxing agents and sensitivity of EDRF-mediated responses to a variety of inhibitors suggest that a single factor or a single common mechanism induces relaxation of vascular smooth muscle. Pharmacological studies have been equivocal with regard to the postulated involvement of phospholipases or arachidonic acid and to the suggestion that EDRF is an oxidative, non-cyclooxygenase product of arachidonate. Experiments on transfer of EDRF and reversal of endothelium-dependent relaxation consistently indicate that EDRF is quite labile. There is convincing evidence that EDRF activates smooth muscle guanylate cyclase, which results in an increase in intracellular cyclic guanosine 3',5'-monophosphate levels. The stimulation of guanylate cyclase by EDRF provides a valuable and sensitive parameter for studies with arteries as well as cells in culture. At present, the identity of EDRF and its role in cardiovascular homeostasis are unknown.
Hypertension
PMID:Endothelium-derived vascular relaxing factor. 298 29

The search for natriuretic hormones or factors by studies of negative pressure breathing, atrial distension experiments, head-out water immersion, expansion of blood volume, Na+/K+-ATPase inhibitors and parabiosis experiments in Dahl rats has led to the finding that the atria are a peptide-secreting endocrine gland. This new natriuretic hormone has now been purified, sequenced and synthetized, and its cDNA and gene have been cloned. The native and synthetic hormones exert identical wide ranging effects (possibly through particulate guanylate cyclase stimulation and adenylate cyclase inhibition) on the kidney, blood vessels, adrenal cortex, and pituitary. Physiopathologic implications of the hormone in experimental hypertension, congestive heart failure, and expansion of blood volume are beginning to emerge.
 ...
PMID:The heart and the atrial natriuretic factor. 298 29

Extracts of mammalian atria, but not ventricles, induce marked diuresis, natriuresis, and reduction in blood pressure when infused systemically in rats and dogs. These extracts also inhibit aldosterone biosynthesis and renal renin release. Natriuretic peptides, 21 amino acids and longer, have been isolated from atria of rodents and man, and share a nearly homologous amino acid sequence at the carboxyterminus. Natriuretic activity resides in a 17-amino acid ring formed by a disulfide bridge, and the C-terminal Phe-Arg appears necessary for full biological potency. The deoxyribonucleic acid-encoding atrial natriuretic peptides have been cloned and the gene structure elucidated. Reduction of the diuretic and natriuretic responses to an acute volume load by right atrial appendectomy first suggested a role for atrial peptides in the physiological response to plasma volume expansion. Subsequently, release of peptides with natriuretic and spasmolytic properties from isolated heart preparations in response to right atrial distension was demonstrated by bioassay and radioimmunoassay. The presence of these peptides in normal rat and human plasma in concentrations of 20-100 pM, and the findings of increased levels in response to acute and chronic plasma volume expansion, rapid atrial tachyarrhythmias, systemic hypertension, congestive heart failure, and renal insufficiency imply that they play an important role in body fluid homeostasis. The mechanisms by which atrial peptides increase renal salt and water excretion are as yet unclear. Renal vascular effects have been consistently demonstrated, and limited evidence for direct actions on tubule ion transport has also been reported recently. In vitro, these peptides cause precontracted vascular and nonvascular smooth muscle to relax, mediated by a direct action on smooth muscle cells. Specific receptors for these peptides have been characterized in crude membranes prepared from whole kidney homogenates and adrenal glomerulosa cells, in intact glomeruli and cultured glomerular mesangial cells, and in intact bovine aortic smooth muscle and endothelial cells. Natriuretic peptides stimulate cyclic guanosine monophosphate accumulation in target tissues, and augment particulate guanylate cyclase activity in membrane fractions, suggesting that cyclic guanosine monophosphate is the second messenger mediating their cellular action.
 ...
PMID:George E. Brown memorial lecture. Role of atrial peptides in body fluid homeostasis. 301 7

Two independent series of biomedical investigations have led to the discovery that the atria are a peptide-secreting endocrine gland. The first is mainly morphological and starts with the finding that mammalian atrial but not ventricular cardiocytes contain "dense bodies". These "dense bodies" later called "specific granules" were found to be different from lysosomes, to be made up of proteins and to incorporate both 3H-leucine and 3-H-fucose in a pattern typical of peptide-secreting endocrine cells. The finding that rat atrial granulation varied with the sodium and water balance led to the crucial observation that atrial extracts have natriuretic and diuretic effects. In less than 4 years, this new natriuretic hormone has been purified, sequenced and synthetized, and its cDNA and gene have been cloned. The ANF gene has been assigned to the distal short arm of chromosome 1 in band 1P36 while the mouse gene is localized in chromosome 4. The native and synthetic hormones exert identical wide ranging effects (possibly through particulate guanylate cyclase stimulation and adenylate cyclase inhibition) on the kidney, blood vessels, adrenal cortex and pituitary. Physiopathologic implications of the hormone in experimental hypertension, congestive heart failure and expansion of blood volume are already beginning to emerge. On the other hand, the search for natriuretic hormones or factors by studies of negative pressure breathing, atrial distention experiments, head-out water immersion, expansion of blood volume, Na+/K-ATPase inhibition and parabiosis experiments in Dahl rats has provided a general framework within which to interpret this new cardiac function.
 ...
PMID:[The heart, an endocrine gland]. 301 75


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