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 renal and hypotensive responses to intravenous infusions of 10, 50, 100, and 200 pmol/kg/min of synthetic rat atrial natriuretic factor (Arg101-Arg-Ser-Ser-Cys-Phe-Gly-Gly-Arg-Ile110-Asp-Arg-Ile-G ly-Ala-Gln-Ser-Gly -Leu-Gly120-Cys-Asn-Ser-Phe-Arg-Tyr; disulfide bond between cysteines) were compared with those produced by synthetic human atrial natriuretic factor (Met110) in five conscious dogs. Increasing doses of rat or human atrial natriuretic factor lowered mean arterial pressure in a dose-related manner. At 200 pmol/kg/min, the maximally effective dose for both peptides, mean arterial pressure was reduced from 116 +/- 4 to 96 +/- 5 mm Hg and from 117 +/- 5 to 100 +/- 3 mm Hg (p less than 0.01), respectively. Neither peptide affected heart rate. Fractional sodium excretion increased from 0.69 +/- 0.22 to 3.95 +/- 1.23% and from 0.69 +/- 0.16 to 4.62 +/- 0.72% during infusions of 200 pmol/kg/min of rat and human atrial natriuretic factor, respectively. Urine volume and fractional chloride excretion rose during infusions of rat or human atrial natriuretic factor in a manner that resembled the elevation in sodium excretion. The stimulation of fractional potassium excretion by both rat and human peptides was more variable and not as clearly dose-dependent. Glomerular filtration rate was enhanced by both rat and human atrial natriuretic factor, while neither peptide significantly changed renal plasma flow.(ABSTRACT TRUNCATED AT 250 WORDS)
Hypertension 1986 Mar
PMID:A comparison of synthetic rat and human atrial natriuretic factor in conscious dogs. 293 82

Evidence for the existence of factor(s) other than blood pressure responsible for modulation of myocardial hypertrophy accompanying hypertension is well documented. A factor that has been isolated from the myocardium of the spontaneously hypertensive rat and partially purified has been shown to stimulate protein synthesis in vitro. Three indexes of protein synthesis, namely incorporation of 3H-leucine into myocyte myosin, specific activity of the leucyl tRNA, and rate of protein synthesis, also were observed to significantly increase on exposure to this factor, which may play a key role in the modulation of myocardial hypertrophy that accompanies hypertension. Evidence has also been presented demonstrating the role of unknown factors that control the shift of myosin isozymes from V1 (a high-ATPase, high-contractile protein type) to V3 (a slow ATPase type myosin), and vice versa. This study demonstrates that the modulation of the myocardial mass can be controlled at different levels: first at an intrinsic intracellular level by the mechanism of a local growth factor, and then at the level of the contractile protein, the quality rather than quantity of which was found to be important. Both of these were observed to be modulated by factor(s) independent of blood pressure and myocardial mass. However, it remains to be determined what is responsible at the genetic level for transmitting the signal that selects what type of protein will be synthesized and whether there is a common pathway among all the controlling factors.
 ...
PMID:Factors regulating myocardial hypertrophy in hypertension. 294 54

alpha-Human atrial natriuretic peptide (hANP) is secreted by the heart and acts on the kidney to promote a strong diuresis and natriuresis. In vivo it has been shown to be catabolized partly by the kidney. Crude microvillar membranes of human kidney degrade 125I-ANP at several internal bonds generating metabolites among which the C-terminal fragments were identified. Formation of the C-terminal tripeptide was blocked by phosphoramidon, indicating the involvement of endopeptidase-24.11 in this cleavage. Subsequent cleavages by aminopeptidase(s) yielded the C-terminal dipeptide and free tyrosine. Using purified endopeptidase 24.11, we identified seven sites of hydrolysis in unlabelled alpha-hANP: the bonds Arg-4-Ser-5, Cys-7-Phe-8, Arg-11-Met-12, Arg-14-Ile-15, Gly-16-Ala-17, Gly-20-Leu-21 and Ser-25-Phe-26. However, the bonds Gly-16-Ala-17 and Arg-4-Ser-5 did not fulfil the known specificity requirements of the enzyme. Cleavage at the Gly-16-Ala-17 bond was previously observed by Stephenson & Kenny [(1987) Biochem. J. 243, 183-187], but this is the first report of an Arg-Ser bond cleavage by this enzyme. Initial attack of alpha-hANP by endopeptidase-24.11 took place at a bond within the disulphide-linked loop and produced a peptide having the same amino acid composition as intact ANP. The bond cleaved in this metabolite was determined as the Cys-7-Phe-8 bond. Determination of all the bonds cleaved in alpha-hANP by endopeptidase-24.11 should prove useful for the design of more stable analogues, which could have therapeutic uses in hypertension.
 ...
PMID:Hydrolysis of alpha-human atrial natriuretic peptide in vitro by human kidney membranes and purified endopeptidase-24.11. Evidence for a novel cleavage site. 297 76

Our study concerned the existence of humoral factor(s) in cardiac hypertrophy arising from experimental perinephritic hypertension in dogs. Hypertension was induced by the method of Page with some modifications. A microassay technique was used on cultured neonatal rat heart cells. Heart extract from the hypertrophied left ventricle of dogs with experimentally induced renal hypertension, but not sham-operated dogs, increased the uptake of 3H-uridine by cultured rat heart cells. At a final heart extract concentration of 5 X 10(-3)% v/v (1-3 micrograms/ml), 3H-uridine was increased by a mean of about 15%, from four experiments. High performance liquid chromatography showed that the heart extract contained at least 16 molecules. Among them, a molecule of approximately 11,200 molecular weight stimulated the uptake of both 3H-uridine and 14C-leucine by cultured rat heart cells. These results indicate that the heart extract from the hypertrophied left ventricle of dogs with experimentally induced renal hypertension contained a factor that might induce and/or modulate myocardial hypertrophy in the model of hypertension.
 ...
PMID:Soluble factor from the hypertrophied left ventricle of dogs in experimental hypertension: ability to stimulate protein metabolism of cultured heart cells. 297 55

Synthetic atrial natriuretic factor (Arg-Arg-Ser-Ser-Cys-Phe-Gly-Gly-Arg-Ile-Asp-Arg-Ile-Gly-Ala-Gln-Ser-Gly -Leu- Gly-Cys-Asn-Ser-Phe-Arg-Tyr-COOH [disulfide bond between cysteines]) was infused intravenously into conscious normotensive and deoxycorticosterone, one-kidney, one-clip, and two-kidney, one-clip hypertensive rats. Mean arterial pressure, urine volume, and electrolyte excretion rates were measured during a 20-minute infusion of a single dose (ranging from 0-1520 pmol/min) into each animal; 95 to 380 pmol/minute of synthetic atrial natriuretic factor maximally reduced mean arterial pressure by -20 +/- 4, -29 +/- 2, and -39 +/- 7 mm Hg in normotensive, one-kidney, one-clip, and two-kidney, one-clip hypertensive rats, respectively. In deoxycorticosterone rats, a dose of 760 pmol/minute was required to produce the largest depressor response (-58 +/- 12 mm Hg). Sodium excretion increased to 8.8 +/- 2.5 muEq/minute at 760 pmol/minute in normotensive rats, to 6.5 +/- 1.1 muEq/minute at 50 pmol/minute in deoxycorticosterone rats, and to 5.8 +/- 1.5 muEq/minute at 95 pmol/minute in one-kidney, one-clip animals. The natriuretic effect was consistently greater at all doses of synthetic atrial natriuretic factor in the two-kidney, one-clip hypertensive model, in which the maximum response was 15.3 +/- 4.7 muEq/minute at 190 pmol/minute. The changes in urine volume and excretion rates of potassium and chloride tended to parallel the increases in sodium excretion in each model. Interestingly, the maximally effective hypotensive dose of synthetic atrial natriuretic factor was different from the maximally effective natriuretic dose in all four groups.(ABSTRACT TRUNCATED AT 250 WORDS)
Hypertension
PMID:Synthetic atrial natriuretic factor in conscious normotensive and hypertensive rats. 298 24

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

The binding of tritiated ligands for various opiate receptor subtypes to brain membranes prepared from spontaneously hypertensive rats and normotensive Wistar-Kyoto rats was determined. The density (Bmax) or the apparent dissociation constant (Kd) for the binding of the mu-ligand (naltrexone) and delta-ligand (Tyr-D-Ser-Gly-Phe-Leu-Thr) to brain membranes of hypertensive and normotensive rats did not differ. However, the Bmax for the binding of kappa-ligand (ethylketocyclazocine, EKC) to brain membranes after the suppression of mu and delta-sites by 100 nM each of unlabeled D-Ala2-MePhe4-Gly-ol5-enkephalin and D-Ala2-D-Leu5-enkephalin, respectively, was significantly greater in hypertensive rats compared to normotensive rats. The Kd values for the binding of 3H-EKC in the two groups did not differ. The binding of 3H-EKC in brain regions was in the order: hypothalamus greater than midbrain greater than striatum greater than cortex greater than pons + medulla. The increase in the binding of 3H-EKC in the brain of hypertensive rats compared to normotensive rats was due to increased binding in the hypothalamus and cortex. These results provide for the first time evidence of selective proliferation of kappa-opiate receptors in the brain of hypertensive rats, and suggest that brain kappa-opiate receptors may play an important role in the pathophysiology of hypertension.
 ...
PMID:Selective proliferation of brain kappa opiate receptors in spontaneously hypertensive rats. 302 39

Two independent series of biomedical investigations have led to the discovery that the atria constitute a peptide-secreting endocrine gland. The first investigation is mainly morphological and started 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 3H-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 five years, this new natriuretic hormone has been purified, sequenced and synthesized, and its CDNA and gene have been cloned. The atrial natriuretic factor (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. Concurrently, the search for the function of natriuretic hormones or factors (through studies of negative pressure breathing, atrial distension 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 as an endocrine gland. 302 9

A lack of correlation between blood pressure and myocardial hypertrophy was established in spontaneously hypertensive rats, suggesting that factors other than blood pressure control might be responsible for the modulation of myocardial hypertrophy. An in vitro system that is independent of blood pressure and hemodynamic effects was developed by use of isolated myocytes to study myocardial protein synthesis. The validity of this system was determined by means of morphology, by receptor integrity, and by studying the incorporation of tritiated leucine into myocyte protein (dpm/mg/hr). Addition of a supernatant of spontaneously hypertensive rat myocardial homogenate (centrifuged at 1500 g) to the myocyte system resulted in a significant increase in tritiated leucine incorporation into myocyte protein when compared with the addition of homogenates from normal controls. The protein from the homogenate was partially purified by high performance liquid chromatography. The resultant purified protein also stimulated protein synthesis by 70%. Furthermore, a significant increase in the specific activity of the transfer RNA and the rate of protein synthesis was observed after addition of homogenate from hypertrophied heart (4.02 +/- 0.3 vs 7.0 +/- 0.2 pmol leucine/microgram protein/hr; p less than 0.05). These data demonstrate the existence of a soluble factor in the hypertrophied myocardium that stimulated protein synthesis. This factor may play a key role in modulation of myocardial structure during development or regression of myocardial hypertrophy in hypertension.
Hypertension 1987 Mar
PMID:A factor that initiates myocardial hypertrophy in hypertension. 302 54

Because several well-studied strains of rats manifest spontaneous hypertension, we set out to design a renin inhibitor suitable for use in this species. On the basis of the sequence of the renin substrate, a series of substrate analogue inhibitory peptides were synthesized by systematically modifying the P5, P3, P2, P1P1', P2', P3', and P4' positions. In assays against rat plasma renin, we found that modifications at the C-terminal segment have a marked influence on potency, and that a secondary butyl side chain at the P2' position is important for obtaining optimal activity. The structure at the P3' position, however, could vary considerably without significant effect. The steric effect of the P2 position was important; there an isopropyl side chain provided optimal binding between the inhibitor and the enzyme. At the P3 and P5 positions, potency appeared to depend on aromatic side chains. The effects at the P1P1' position of the transition-state residue (3S,4S)-4-amino-3-hydroxy -6-methylheptanoic acid (statine) and its congeners (3S,4S)-4-amino-3-hydroxy-5-phenylpentanoic acid (AHPPA) and (3S,4S)-4-amino-3-hydroxy-5-cyclohexylpentanoic acid (ACHPA) were found to depend on the sequence of the C-terminal segment. For peptides with an unfavorable C-terminal segment (-Ile-Phe-NH2), AHPPA and ACHPA resulted in a surprising retention of potency. For peptides with a favorable C-terminal segment (-Leu-Phe-NH2), the effect of AHPPA was mild, even though ACHPA still significantly enhanced potency. The hypotensive and plasma renin inhibitory effects of three of the analogues were then studied in anesthetized sodium-depleted rats. One of the compounds, acetyl-His-Pro-Phe-Val-Statine-Leu-Phe-NH2 (IC50 against rat plasma renin of 30 nM at pH 7.4), proved to be a potent hypotensive agent and a potentially useful probe for the study of the renin-angiotensin system in rats.
 ...
PMID:Design of rat renin inhibitory peptides. 304 20


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