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)

In patients with severe hypertension and in age and sex matched controls the circulating levels of calcitonin gene-related peptide-like immunoreactivity (CGRP-LI) and substance P-LI were measured. Samples were taken before medication, after 2-4 weeks and 2-12 months of pharmacological treatment to normotension. In the control group CGRP-LI levels were significantly higher for females than for males. No such relation was seen for substance P-LI. There were no correlations between CGRP-LI, substance P-LI or blood pressure. In the untreated acute hypertensive group there was a significant correlation between circulating levels of CGRP-LI and both diastolic and systolic blood pressure. No such relationship was seen for substance P-LI. The plasma levels of substance P-LI were significantly elevated (2.8 +/- 4.0) compared to controls (1.3 +/- 1.3, pmol/l, mean +/- S.D., p < 0.01). The levels of CGRP-LI did not differ from the control group. After 2-4 weeks of treatment the blood pressure decreased significantly and the plasma levels of substance P-LI were normalized while the CGRP-LI still did not differ from that of controls. After 2-12 months of treatment the blood pressure was still normalized, and the plasma levels of CGRP-LI and substance P-LI were not different from the control group. In the present study there was a positive correlation in hypertensives between the circulating CGRP-LI levels and diastolic and systolic blood pressure and elevated levels of substance P-LI. This would implicate the existence of a dynamic control through which the sensory system may register and damp the pressure response.
 ...
PMID:Sensory nerve terminal activity in severe hypertension as reflected by circulating calcitonin gene-related peptide (CGRP) and substance P. 128 70

Age-related changes in CGRP-containing vasodilator nerve activity in hypertension were studied in perfused mesenteric vascular beds isolated from SHR and normotensive rats (WKY). Perivascular nerve stimulation (PNS; 0.5-8 Hz) of both SHR and WKY preparations with active tone produced a frequency-dependent vasodilator response, which was abolished by 100 nM tetrodotoxin, 500 nM capsaicin or cold storage denervation. This response in SHR greatly decreased with age, whereas the response in WKY slightly decreased with age. The neurogenic vasodilation in 15- and 30-week-old SHR but not 8-week-old SHR was significantly smaller than that in age-matched WKY. Vasodilator responses to exogenous CGRP (0.1-30 nM) in SHR increased with age, whereas an age-related decrease in the vasodilation was found in WKY. Immunohistochemical studies showed an age-related decrease in CGRP-containing fibers in SHR. These results suggest that CGRP-containing vasodilator innervation is greatly decreased when SHR develop and maintain hypertension.
 ...
PMID:Age-related changes in calcitonin gene-related peptide (CGRP)-mediated neurogenic vasodilation of the mesenteric resistance vessel in SHR. 177 6

Little is known of the significance of perivascular peptides in hypertension. In this study we have investigated the circulating levels of calcitonin gene-related peptide-like immunoreactivity (CGRP-LI) and substance P- like immunoreactivity (SP-LI) during and after treatment of severe hypertension. Seventeen patients with a mean blood pressure of 204/127 mmHg were included. Circulating levels of CGRP-LI and SP-LI in normotensive controls were 35 +/- 4 and 1.2 +/- 0.1 pmol/l, respectively. In the hypertensives CGRP-LI was significantly lower (22 +/- 3 pmol/l: P less than 0.05) while SP-LI did not differ (1.6 +/- 0.3 pmol/l) from the normotensives. After treatment the circulating level of CGRP-LI was still significantly lower (16 +/- 2 pmol/l: P less than 0.001) while SP-LI remained unchanged when compared with the controls. These observations suggest an involvement of vascular afferent nerves in the aetiology of hypertension in man.
 ...
PMID:Reduced levels of calcitonin gene-related peptide (CGRP) but not substance P during and after treatment of severe hypertension in man. 247 45

With the techniques of specific radioimmunoassay and gel filtration it was found that CGRP was distributed in various tissues of normotensive (WKY) and spontaneously hypertensive rats (SHR) with the highest concentration in the lumbar spinal cord (1197 +/- 94.8 pg/mg tissue) and the lowest in the auricle (15.0 +/- 2.1 pg/mg tissue). In comparison with WKY, CGRP concentration in the plasma was decreased and in the abdominal aorta and hypothalamus was increased in SHR. Gel filtration revealed only one major CGRP molecular form in the tissues. In addition, CGRP reduced the mean arterial pressure (MAP) in SHR in a dose-dependent manner. These data suggest that CGRP may play an important role in the pathogenesis of hypertension and its possible therapy.
 ...
PMID:Calcitonin gene-related peptide (CGRP) in normotensive and spontaneously hypertensive rats. 278 8

The present study was undertaken to examine the effect of parathyroid hormone-related peptide (PTHrP) on the vascular tone as well as the expression of its mRNA in the cardiovascular system and its regulation in response to systemic hypertension in Sprague-Dawley rats. In aortic rings precontracted with 0.3 microM norepinephrine PTHrP(1-34) caused a dose-dependent relaxation with the maximal response of 33% being observed at 10(-6) M. PTHrP was nearly equipotent to PTH or CGRP in the vasodilatory action. Ribonuclease protection assay and Northern blot analysis demonstrated that PTHrP mRNA levels in the heart and aorta were increased as a result of systemic hypertension induced by constant infusion of angiotensin II and salt loading. The results of our in vivo studies suggest an autocrine/paracrine role for PTHrP as a local regulator of the vascular tone.
 ...
PMID:Parathyroid hormone-related peptide as a locally produced vasorelaxant: regulation of its mRNA by hypertension in rats. 788 63

More than 80 studies have reported lowered blood pressure after dietary calcium enrichment in experimental models of hypertension. The evidence presented here suggests that dietary calcium may act concurrently through a number of physiological mechanisms to influence blood pressure. The importance of any given mechanism may vary depending on the experimental model under consideration. Supplemental dietary calcium is associated with reduced membrane permeability, increased Ca(2+)-ATPase and Na,K-ATPase, and reduced intracellular calcium. These results suggest that supplemental calcium may limit calcium influx into the cell and improve the ability of the VSMC to extrude calcium. This could be a direct effect of calcium on the VSMC or an indirect effect mediated hormonally. The calcium-regulating hormones have all been found to have vasoactive properties and therefore may influence blood pressure. Furthermore, CGRP and the proposed parathyroid hypertensive factor are both vasoactive substances that are responsive to dietary calcium. Therefore, diet-induced variations in calcium-regulating hormones may influence blood pressure. Modulation of the sympathetic nervous system is another important way that dietary calcium can influence blood pressure. There is evidence of altered norepinephrine levels in the hypothalamus as a consequence of manipulations of dietary calcium as well as changes in central sympathetic nervous system outflow. Dietary calcium has also been shown to specifically modify alpha 1-adrenergic receptor activity in the periphery. In some experimental models of hypertension, dietary calcium may alter blood pressure by changing the metabolism of other electrolytes. For example, the ability of calcium to prevent sodium chloride-induced elevations in blood pressure may be attributed to natriuresis. However, natriuresis does not account for all of the interactive effects of calcium and sodium chloride on blood pressure. Sodium chloride-induced hypertension may be due in part to calcium wasting and subsequent elevation of calcium-regulating hormones. Chloride is an important mediator of this effect because it appears that sodium does not cause calcium wasting when it is not combined with chloride. More attention to the central nervous system effects of dietary calcium is needed. Not only can calcium itself influence neural function, but many of the calcium-regulating hormones appear to affect the central nervous system. The influence of calcium and calcium-regulating hormones on central nervous system activity may have important implications for blood pressure regulation and also may extend to other aspects of physiology and behavior.
Hypertension 1994 Apr
PMID:Dietary calcium and blood pressure in experimental models of hypertension. A review. 814 21

In anesthetized rats we examined whether calcitonin gene-related peptide activated renal pelvic sensory receptors and, if so, whether activation of renal pelvic calcitonin gene-related peptide receptors contributes to the inhibitory renorenal reflex response to renal mechanoreceptor stimulation. Calcitonin gene-related peptide (0.0026, 0.026, 0.26, and 2.6 mumol/L) administered into the renal pelvis increased ipsilateral afferent renal nerve activity in a concentration-dependent fashion (32 +/- 14%, 69 +/- 19%, 93 +/- 26%, and 253 +/- 48% [all P < .01], respectively). The increases in ipsilateral afferent renal nerve activity elicited by calcitonin gene-related peptide were associated with increases in contralateral urinary sodium excretion. The calcitonin gene-related peptide receptor antagonist human CGRP (h-CGRP) (8-37) (0.01, 0.1, 1.0, and 10 mumol/L) decreased the ipsilateral afferent renal nerve activity response to renal pelvic administration of calcitonin gene-related peptide (0.26 mumol/L) in a concentration-dependent fashion (29 +/- 4%, 33 +/- 12%, 76 +/- 9% [P < .01], and 86 +/- 13% [P < .01], respectively). In the presence of renal pelvic perfusion with vehicle, an increase in ureteral pressure of 5, 10, and 20 mm Hg increased ipsilateral afferent renal nerve activity by 13 +/- 7%, 41 +/- 7% (P < .01), and 95 +/- 15% (P < .01) and contralateral urinary sodium excretion by 8 +/- 1%, 24 +/- 4%, and 42 +/- 7% (all P < .05). The ipsilateral afferent renal nerve activity and contralateral natriuretic responses to graded increases in ureteral pressure (5 to 20 mm Hg) were unaltered by renal pelvic perfusion with h-CGRP (8-37) at 1.0 and 10 mumol/L.(ABSTRACT TRUNCATED AT 250 WORDS)
Hypertension 1994 Jun
PMID:Renal sensory receptor activation by calcitonin gene-related peptide. 820 95

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.
 ...
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.
 ...
PMID:Augmented sensory-motor vasodilatation of the rat mesenteric arterial bed after chronic infusion of the P1-purinoceptor antagonist, DPSPX. 884 31

Adrenomedullin (AM), a potent vasodilator peptide, exists in the cardiac ventricle; however, the role of AM in the ventricular tissue remains unknown. In the present study, we investigated the production and secretion of AM in cultured neonatal rat cardiomyocytes, and we examined the effect of AM on de novo protein synthesis in these cells by measuring [14C]phenylalanine incorporation. The cardiomyocytes cultured with serum-free media secreted AM into the media in a time-dependent manner at the rate of 12.2+/-0.5 fmol/10(5) cells/48 hours (mean+/-SEM). Angiotensin II (1 micromol/L) or 10% fetal bovine serum significantly (P<.01) increased the AM secretion by 115% and 305%, respectively. In addition, Northern blot analysis of total RNA extracted from the myocytes disclosed the expression of prepro-AM mRNA of 1.6 kb. Synthetic AM at 1 micromol/L significantly reduced the 10(-6) mol/L angiotensin II- and 10% fetal bovine serum-stimulated [14C]phenylalanine incorporation into the cells, by 16% (P<.05) and 20% (P<.01), respectively. The inhibitory effect of AM on the angiotensin II-stimulated [14C]phenylalanine incorporation was abolished dose-dependently by a calcitonin gene-related peptide receptor antagonist, CGRP(8-37). Furthermore, blockade of the action of endogenous AM by either 10(-6) mol/L CGRP(8-37) or anti-AM monoclonal antibody significantly enhanced the basal and 10(-6) mol/L angiotensin II-stimulated [14C]phenylalanine incorporation. In summary, cultured neonatal rat cardiomyocytes produce and secrete AM, and the secreted AM inhibits the protein synthesis of these cells. Thus, AM may act on cardiomyocytes as an autocrine or a paracrine factor modulating the cardiac growth.
Hypertension 1998 Jan
PMID:Adrenomedullin: a possible autocrine or paracrine inhibitor of hypertrophy of cardiomyocytes. 945 53


1 2 3 4 Next >>