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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Data are presented concerning the basal levels of parathormone and calcitonin and the effect of dihydropyridine derivatives on the characteristics of haemodynamics as well as pancreatic secretory activity in patients with diabetes mellitus. It is shown that in diabetic patients with hypertension a single administration of the drugs induces vasodilatation which causes lowering of systolic and diastolic blood pressure. In patients with diabetes mellitus in combination with hypertension, heart coronary disease and obvious peripheral angiopathy (similar procedure) no peripheral vasodilatation was observed. No negative effects were observed on the compensatory processes (and obviously on pancreatic secretory activity in patients with both insulin-dependent and insulin-independent diabetes mellitus even during long-lasting administration of drugs. A conclusion is made that calcium channel antagonists should be recommended to patients with diabetes mellitus taking into account the state of their peripheral vessels.
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PMID:[Effect of calcium antagonists on the hemodynamic and pancreatic secretory parameters in diabetes mellitus]. 840 42

Calcitonin gene-related peptide, a product of the calcitonin gene, is a potent vasodilator neuropeptide. We have demonstrated that dietary calcium deficiency decreased the neuronal (laminae I/II of the dorsal horn of the spinal cord) content of immunoreactive calcitonin gene-related peptide in the normal rat. Neuronal calcitonin gene-related peptide levels are also reduced in the spontaneously hypertensive rat, a model characterized by calcium deficiency. However, the mechanism of this reduction in neuronal calcitonin gene-related peptide could be due to decreased synthesis or increased release. To determine if neuronal calcitonin gene-related peptide messenger RNA (mRNA) levels are also decreased in the spontaneously hypertensive rat, we measured relative calcitonin gene-related peptide mRNA levels (using a genomic hybridization probe specific for alpha- and beta-calcitonin gene-related peptide mRNA) in dorsal root ganglia from spontaneously hypertensive and Wistar-Kyoto control rats. Dorsal root ganglia neuronal cell bodies are a prominent site of calcitonin gene-related peptide synthesis and send axons to peripheral blood vessels and central spinal cord sites (laminae I/II). After normalization of calcitonin gene-related peptide mRNA levels of 18S RNA, the calcitonin gene-related peptide mRNA/18S RNA ratio was significantly decreased approximately threefold in the spontaneously hypertensive rats compared with controls. This alteration in calcitonin gene-related peptide mRNA levels is specific for dorsal root ganglia, because no strain differences in calcitonin gene-related peptide mRNA content were detected in heart or brain.(ABSTRACT TRUNCATED AT 250 WORDS)
Hypertension 1993 Jun
PMID:Calcitonin gene-related peptide gene expression in the spontaneously hypertensive rat. 850 84

We recently established that the chronic inhibition of nitric oxide production with NG-nitro-L-arginine methyl ester (L-NAME) increases blood pressure and fetal mortality in pregnant rats. Using this animal model, we have investigated whether calcitonin gene-related peptide (CGRP) can reverse the pre-eclampsia-like conditions produced by L-NAME. CGRP and L-NAME were chronically infused s.c. into pregnant rats separately or together starting on day 17 of gestation; a control group was given saline infusions. Systolic blood pressure was measured on gestational days 17, 18, 19 and 22 and post-partum days 1 and 2. The weight and mortality of the pups were recorded immediately after spontaneous delivery. Animals treated with L-NAME exhibited significant elevations of blood pressure on days 18, 19 and 22 of gestation and during post-partum, increased pup mortality (18.4 versus 0.0%) and decreased pup weights (5.14 ± 0.07 versus 6.20 ± 0.06 g). The co-administration of L-NAME and CGRP prevented the gestational (not the post-partum) L-NAME hypertension and decreased pup mortality to 6.4% but did not reverse the decreased fetal weight (5.31 ± 0.06 g). Our data indicate that CGRP (i) participates in regulation of the vascular adaptations that occur during normal pregnancy, (ii) has beneficial effects on the hypertension and increased mortality of experimental preeclampsia, and (iii) may exert differential effects on the systemic (i.e. maternal) and fetal components of uteroplacental circulation. These findings may have important clinical implications. Keywords: CGRP/nitric oxide/pre-eclampsia/pregnancy/progesterone
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PMID:Calcitonin gene-related peptide reverses the hypertension and significantly decreases the fetal mortality in pre-eclampsia rats induced by NG-nitro-Lmethyl ester 867 48

We recently established that the chronic inhibition of nitric oxide production with N(G)-nitro-L-arginine methyl ester (L-NAME) increases blood pressure and fetal mortality in pregnant rats. Using this animal model, we have investigated whether calcitonin gene-related peptide (CGRP) can reverse the pre-eclampsia-like conditions produced by L-NAME. CGRP and L-NAME were chronically infused s.c. into pregnant rats separately or together starting on day 17 of gestation; a control group was given saline infusions. Systolic blood pressure was measured on gestational days 17, 18, 19 and 22 and post-partum days 1 and 2. The weight and mortality of the pups were recorded immediately after spontaneous delivery. Animals treated with L-NAME exhibited significant elevations of blood pressure on days 18, 19 and 22 of gestation and during post-partum, increased pup mortality (18.4 versus 0.0%) and decreased pup weights (5.14 +/- 0.07 versus 6.20 +/- 0.06 g). The co-administration of L-NAME and CGRP prevented the gestational (not the post-partum) L-NAME hypertension and decreased pup mortality to 6.4% but did not reverse the decreased fetal weight (5.31 +/- 0.06 g). Our data indicate the CGRP (i) participates in regulation of the vascular adaptations that occur during normal pregnancy, (ii) has beneficial effects on the hypertension and increased mortality of experimental preeclampsia, and (iii) may exert differential effects on the systemic (i.e. maternal) and fetal components of utero-placental circulation. These findings may have important clinical implications.
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PMID:Calcitonin gene-related peptide reverses the hypertension and significantly decreases the fetal mortality in pre-eclampsia rats induced by N(G)-nitro-L-arginine methyl ester. 872 98

125I-labeled rat amylin binds to specific sites in the cortex of rat kidney, which can be distinguished from those for 125I-labeled salmon calcitonin (sCT) and 125I-labeled rat alpha-calcitonin gene-related peptide (alpha-CGRP) on the basis of regional distribution. These sites have a high affinity (approximately 1 nM) for amylin, and 125I-amylin binding is potently inhibited by the peptide antagonists AC413 and sCT-(8-32), whereas CGRP-(8-37) is a poor inhibitor of binding. Furthermore, incubation with guanosine 5'-O-(3-thiotriphosphate) (GTP gamma S) inhibits 125I-amylin binding by > 90%, indicating that binding is dependent on coupling to G proteins. In renal cortex, amylin stimulated adenylyl cyclase activity three- to fourfold, and this was inhibited by AC413 and sCT-(8-32) but not by CGRP-(8-37). Amylin activated plasma renin twofold, and this was blunted by prior administration of AC413 but not CGRP-(8-37). We speculate that amylin may play an important role in renal physiology and that in states of hyperamylinemia, as found in obesity and the insulin resistance syndrome, this peptide may be involved in the genesis and development of hypertension.
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PMID:Amylin binding in rat renal cortex, stimulation of adenylyl cyclase, and activation of plasma renin. 877 89

1. The effect of long-term antagonism of P1-purinoceptors on vascular function was examined in the perfused mesenteric arterial bed isolated from rats which had received constant infusion of either the non-selective P1-purinoceptor antagonist, 1-3-dipropyl-8-sulphophenylxanthine (DPSPX, 30 micrograms kg-1 h-1, i.p.) or saline for seven days. Sympathetic and sensory-motor neurotransmission, smooth muscle and endothelial function were assessed. 2. Basal tone was similar in mesenteric arterial preparations from control and DPSPX-treated rats. Continuous perfusion with methoxamine (7-70 microM) induced similar increases in tone in control and DPSPX-treated preparations. In the presence of guanethidine (5 microM), electrical field stimulation (EFS; 1-12 Hz, 60V, 0.1 ms, 30 s) elicited frequency-dependent vasodilatation due to activation of sensory-motor nerves. In tissues from DPSPX-treated rats the nerve-mediated vasodilator responses were markedly augmented at all frequencies. Maximal relaxation at 8 Hz was 38.34 +/- 4.76% (n = 5) in controls and 65.92 +/- 3.68% (n = 5) after DPSPX-treatment (P < 0.01). Adenosine (3 microM) inhibited the frequency-dependent sensory-motor neurotransmission similar in preparations from controls and DPSPX-treated rats. 3. In raised-tone preparations calcitonin gene-related peptide (CGRP; 5,15 and 50 pmol), the principal vasodilator transmitter of sensory-motor nerves in rat mesenteric arteries, produced similar relaxations in control and DPSPX-treated preparations. Vasodilator responses to the sensory neurotoxin capsaicin (50 and 500 pmol) were also similar between the groups. 4. Assay of tissue CGRP levels of the superior mesenteric artery by enzyme-linked immunosorbent assay showed no significant difference in tissue levels of CGRP in controls, 120.25 +/- 26.34 pmol g-1 tissue (n = 6) and with DPSPX-treatment, 82.12 +/- 24.42 pmol g-1 tissue (n = 6). 5. In raised-tone preparations dose-dependent endothelium-dependent vasodilatation to acetylcholine and ATP, and endothelium-independent vasodilatation to sodium nitroprusside were similar in control and DPSPX-treated preparations. 6. EFS (4-32 Hz, 90V, 1 ms, 30 s) elicited frequency-dependent vasoconstriction due to activation of sympathetic nerves which was similar in controls and in DPSPX-treated preparations. Adenosine (10 and 30 microM) inhibited sympathetic neurotransmission similarly in control and DPSPX-treated preparations. Dose-dependent vasoconstriction to noradrenaline (NA) and ATP, and to KCI (0.15 mmol) was similar between the groups. 7. High performance liquid chromatographic analysis of tissue NA showed no significant difference in NA content of the superior mesenteric artery from DPSPX-treated (1.38 +/- 0.09 ng mg-1, n = 6) and control rats (1.46 +/- 0.17 ng mg-1, n = 6). 8. In conclusion, in rats with hypertension due to 7 days treatment with the P1-purinoceptor antagonist, DPSPX, there is an increase in sensory-motor vasodilatation of the mesenteric arterial bed. There is no change in sympathetic nerve, endothelial or smooth muscle function. Augmented sensory-motor neurotransmission, which does not involve a change in postjunctional responsiveness to CGRP or in the CGRP content of sensory-motor nerves, could be a compensatory change in response to the DPSPX- induced hypertension.
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PMID:Augmented sensory-motor vasodilatation of the rat mesenteric arterial bed after chronic infusion of the P1-purinoceptor antagonist, DPSPX. 884 31

Human adrenomedullin, a novel hypotensive peptide, contains a six-member ring structure similar to that found in calcitonin gene-related peptide and pancreatic amylin. Unlike the full-sequence peptide, human adrenomedullin-(15-22) [hADM-(15-22)], which contains the ring structure, increases systemic arterial pressure in the rat but not the cat. We undertook the present study to investigate the mechanism by which hADM-(15-22) increases systemic arterial pressure in the rat. Injection of hADM-(15-22) in doses of 10 to 300 nmol/kg i.v. increased systemic arterial pressure in a dose-dependent manner and was threefold less potent than norepinephrine when doses were compared on a nanomole basis. However, the ring structures of human calcitonin gene-related peptide and human amylin, human calcitonin gene-related peptide-(1-8) and human amylin-(1-8), respectively, had no significant effect on systemic arterial pressure in the rat. Pressor responses to hADM-(15-22) were reduced significantly after administration of phentolamine or reserpine. Responses to hADM-(15-22) were not altered by the angiotensin type 1 blocking agent DuP 753 or the endothelin-A/endothelin-B receptor blocking agent bosentan, and responses to hADM-(15-22) and the nicotinic agonist 1,1-dimethyl-4-phenylpiperazinium (DMPP) were reduced after bilateral adrenalectomy. Pressor responses to DMPP were reduced by hexamethonium, whereas the nicotinic blocking agent had no effect on the pressor response to hADM-(15-22). These data suggest that increases in systemic arterial pressure in response to hADM-(15-22) in the rat are mediated by the activation of alpha-adrenergic receptors by catecholamines released from the adrenal medulla. The present data suggest that hADM-(15-22) releases catecholamines from the adrenal medulla by a noncholinergic mechanism.
Hypertension 1996 Dec
PMID:Catecholamine release mediates pressor effects of adrenomedullin-(15-22) in the rat. 895 94

The syndrome of insulin resistance comprises the following H-phenomena: 1. Hyperinsulinism compensating the inborn postreceptor insulin resistance, 2. Hyperglycaemia-non-insulin-dependent diabetes mellitus, 3. Hyperlipoproteinaemia with android obesity, 4. Hypertension, 5. Hirsutism with the syndrome of polycystic ovaries as a manifestation of a hyperandrogenic situation in the female organism. Molecular syndromes of this syndrome of insulin resistance are obscure. They are the subject of intensive studies because H-phenomena are an aggregation of the main risk factors of atherogenesis. Recently attention is focused also on amylin--a 37 amino acid peptide with a 50% homologous amino acid sequence with a calcitonin-gene--related peptide (CGRP), which is the product of a gene made up of three introns on the 12th chromosome. Amylin acts in the beta-cells of the pancreas as a co-secretion of insulin. If in excess, it is deposited in the form of an amyloid in the beta-cells. In the early stage of NIDDM it alters the physiological response of the beta-cell to glycaemic stimuli and food, in later stages of the disease, after accumulation, it causes apoptosis of the beta-cell and reduces thus the secretory capacity of the Langerhans islets. It is excreted in the urine and thus, if the glomerular filtration is reduced, it cumulates in the blood stream and thus enhances insulin resistance already in the early stages of chronic renal insufficiency, or in diabetic nephropathy. In type II diabetes similarly as insulin levels also amylin levels are elevated, while in type I diabetes with early autoimmune destruction of the beta-cells the insulin and amylin levels are reduced or even zero. Amylin reduces in the muscle, probably by inhibition of glycogen synthase, the insulin stimulated non-oxidative utilization of glucose into muscle glycogen and conversely by stimulation of phosphorylase it stimulates glycogenolysis and thus also lactate production and gluconeogenesis in the liver which all are anti-insulin effects which intensify the insulin resistance of the main target tissues. Amylin, similarly as CGRP or calcitonin, reduces Ca blood levels and has a vasodilatating effect; it reduces the BP but in different minimal and maximal doses and by a different mechanism and via special receptors because the link of amylin to calcitonin receptors is 100 times lower and does not produce a rise of cAMP in the target cell. The effect on the enhancement of insulin resistance in muscle was proved also by direct measurements using an hyperinsulinaemic euglycaemic clamp. After prolongation of the clamp to more than two hours the effect on insulin resistance disappeared, although the hypocalcinaemic effect persisted. Amylin is able by its biological action to modify the secretion as well as the effectiveness of insulin to pathological values. These two characteristics are typical for impaired glucose tolerance in type II diabetes. Studies are under way to find out whether the effect of amylin is involved directly also in the pathogenesis of the other H-phenomena or only via accentuation of hyperinsulinism. In any case amylin is a new link the role of which in the pathogenesis of NIDDM and the syndrome of insulin resistance awaits evaluation. Due to its effect on gastric evacuation it participates also in the postprandial glycaemic control in particular in type I diabetes where it it begins to be used in therapy. Perhaps it will be possible to administer it in these patients along with insulin to improve diabetes compensation.
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PMID:[Amylin as an additional possible pathogenic factor in NIDDM and the insulin resistance syndrome]. 896 27

Inhibition of nitric oxide production with NG-nitro-L-arginine methyl ester (L-NAME) increases blood pressure and fetal mortality in pregnant rats. We previously reported that administration of calcitonin gene-related peptide (CGRP) reduces the blood pressure and fetal death produced by L-NAME. To determine the hemodynamic role of endogenous CGRP in this setting, CGRP8-37, a CGRP receptor antagonist, was used. In addition, CGRP mRNA and peptide levels were determined in dorsal root ganglia. L-NAME or control rats had intravenous (for drug administration) and arterial (for continuous mean blood pressure monitoring) catheters surgically placed and were studied in the conscious unrestrained state. Baseline blood pressure was higher in the L-NAME than the control rats on days 19, 20, and 21 or pregnancy and postpartum day 1. Vehicle administration did not change blood pressure in any group, and CGRP8-37 (100 micrograms) did not change blood pressure in control groups. However, CGRP8-37 administration to the L-NAME rats further increased blood pressure (P < .05) on days 19 (8 +/- 1), 20 (12 +/- 2), and 21 (7 +/- 1) of gestation but was without effect on postpartum day 1. Furthermore, CGRP mRNA or peptide levels in dorsal root ganglia were not different between the L-NAME and control rats at any of the time points studied. These data indicate that in experimental preeclampsia, CGRP is playing a compensatory vasodilator role to attenuate the elevated blood pressure. The mechanism of this effect appears to be an enhanced vascular responsiveness to CGRP that is attenuated after the birth of pups.
Hypertension 1997 Jan
PMID:Calcitonin gene-related peptide is a depressor in NG-nitro-L-arginine methyl ester-induced hypertension during pregnancy. 903 10

Amylin (or islet amyloid polypeptide) has been reported to have binding sites in the central nervous system and the kidney and has been shown to activate plasma renin. It has been postulated that this peptide may be an important mechanistic link between hypertension and diabetes in the insulin resistance syndrome. To explore this issue, the effects of rat amylin on mean arterial blood pressure were investigated in anaesthetised rats. Amylin elicited a pressor response of approximately 10 mmHg (maximal at 100 pmol.kg-1) which was apparent within 30-60 s and persisted over 15 min. At higher concentrations amylin elicited a hypotensive response (negative log IC50 8.52 mol.kg-1). The novel amylin receptor antagonist AC413 (12 nmol.kg-1.min-1) reduced the pressor response but not the hypotensive effects of amylin. The peptide antagonist calcitonin gene-related peptide (CGRP)8-37 (12 nmol.kg-1.min-1) reduced the pressor response elicited by amylin and also antagonized the hypotensive effect of amylin. Pre-treatment of animals with the ganglion blocker mecamylamine (3 mg.kg-1 s.c.) reduced the pressor effect of amylin. Following the administration of the angiotensin converting enzyme inhibitor ramiprilat (300 nmol.kg-1 i.v.) the pressor response to amylin was reduced. Salmon calcitonin also elevated blood pressure in the anaesthetised rat; doses of amylin and salmon calcitonin associated with a pressor effect were associated with increases in plasma renin activity. We conclude that amylin may act centrally to elevate blood pressure in the anaesthetised rat, possibly through activation of the renin angiotensin system.
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PMID:Rat amylin mediates a pressor response in the anaesthetised rat: implications for the association between hypertension and diabetes mellitus. 908 62


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