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

Neuropeptide Y (NPY), first isolated in 1982, is widely distributed among the neurons of the central and peripheral nervous systems, often in close association with catecholamines. Because of its wide distribution and concentrations in selected areas of the brain, NPY is considered a putative neurotransmitter with several possible physiological effects including modulation of blood pressure, food intake and pituitary hormone release at a central level. Peripherally, the peptide seems to be involved, via direct and indirect mechanisms, in noradrenaline (NA)-mediated vasoconstriction. The ability of NPY to interact with the catecholamine transmission line may underly a possible modulatory influence of NPY on catecholamine receptor characteristics. We recently observed interaction between alpha-2 adrenergic receptors and those for NPY at the presynaptic level. Additional data from our studies in spontaneously hypertensive rats suggest that impairment of these interactions may contribute to the hypertension in this strain.
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PMID:Neuropeptide Y interaction with the adrenergic transmission line: a study of its effect on alpha-2 adrenergic receptors. 132 37

A high salt diet leads to up-regulation of alpha-2 adrenoceptors and down-regulation of beta-2 adrenoceptors in normotensive subjects. Although the increase in blood pressure with a high salt diet is not related to the magnitude of the alpha-2 or beta-2 adrenoceptor changes alone, it is related to the increase in the ratio of the receptor changes (operative alpha/beta adrenoceptor ratio). An increase in the operative alpha/beta adrenoceptor ratio with a high salt intake results in vasoconstriction and reduced vasodilatation at resistance vessels, as well as increased renal proximal tubular sodium reabsorption. An influence of heredity on this relationship is supported by four lines of evidence: 1) salt-sensitivity of blood pressure occurs predominantly in subjects with a family history of hypertension; 2) studies in twin children document the influence of genetic variance on salt-sensitivity of blood pressure; 3) subjects with a family history of hypertension have a significantly lower salivary sodium concentration and an altered urinary sodium excretion after salt loading compared to subjects with no such history; 4) salt-sensitivity of blood pressure may be associated with specific genetic markers. On the basis of these observations, we propose the hypothesis that enhanced inverse alpha-beta-adrenoceptor regulation in response to a high salt intake may be responsible for salt sensitivity in the normal population, and may contribute to the development of essential hypertension in susceptible individuals. This alteration is likely to be genetically mediated.
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PMID:Inverse regulation of alpha-2 and beta-2 adrenoceptors in salt-sensitive hypertension: an hypothesis. 255 14

Beta adrenoceptor-mediated relaxation was studied on femoral and mesenteric arteries and thoracic aorta from deoxycorticosterone-salt hypertensive and age-matched normotensive rats. Maximum relaxations to isoproterenol (ISO), fenoterol and norepinephrine were less in hypertensive than in normotensive tissues. Mean negative log EC50 values of ISO and norepinephrine, but not fenoterol, were smaller in femoral and mesenteric strips from hypertensive rats than those from oil-water-treated rats. In thoracic aortas from hypertensive rats, the mean negative log EC50 values of ISO and fenoterol decreased, whereas those of norepinephrine increased as compared with those in oil-water-treated rats. In oil-salt- and deoxycorticosterone-water-treated rats, hypertension did not develop nor were the responses to ISO reduced. Relative potencies of the beta adrenoceptor agonists and Schild plot data for atenolol and butoxamine indicate that femoral arteries of normotensive and hypertensive rats possess beta-1 adrenoceptors mediating relaxation. It also is suggested that the mesenteric artery and thoracic aorta of both normotensive and hypertensive rats predominantly possess beta-2 adrenoceptors mediating relaxation. The present results suggest that an elevation in blood pressure is associated with the reduction of beta-1 adrenoceptor-mediated relaxation in femoral arteries and of beta-2 adrenoceptor-mediated relaxation in mesenteric arteries.
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PMID:Altered vascular beta adrenoceptor-mediated relaxation in deoxycorticosterone-salt hypertensive rats. 283 51

The effects of chronic elevation of plasma epinephrine concentrations on pressor and cardiac chronotropic responses to spinal stimulation and exogenous norepinephrine were studied in the pithed rat. Animals were treated s.c. with epinephrine (100 micrograms/kg/hr) or vehicle for 6 days. Treatment with epinephrine resulted in hypertension. Epinephrine treatment significantly reduced pressor and cardiac chronotropic responses to norepinephrine. This treatment also reduced cardiac chronotropic responses to spinal stimulation but had no significant effect on pressor responses to spinal stimulation. The preferential beta-2 adrenoceptor antagonist ICI 118,551 (50 micrograms/kg) had no effect on pressor or cardiac chronotropic responses to norepinephrine in either vehicle-treated or epinephrine-treated animals. Similarly, pressor responses to spinal stimulation were unaffected in the vehicle-treated group. However, ICI 118,551 significantly reduced pressor responses to spinal stimulation after epinephrine treatment. Chronic epinephrine treatment also resulted in accumulation of epinephrine in the heart, kidneys and aorta. However, epinephrine accumulation in the heart was much greater than in the kidney or aorta. Acute infusion of epinephrine, which produced plasma epinephrine concentrations similar to those observed in the chronically treated animals, caused a reduction of pressor and cardiac chronotropic responses to both nerve stimulation and norepinephrine. In conclusion, chronic epinephrine treatment led to accumulation of epinephrine in peripheral tissues and to the development of a facilitatory influence of beta-2 adrenoceptors on pressor responses to nerve stimulation in the pithed rat that were not observed in vehicle-treated animals. The authors believe that this influence is prejunctional in nature.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Cardiovascular responsiveness to sympathetic activation after chronic epinephrine administration. 287 35

This report reviews a number of significant developments in the fields of noradrenergic transmission and adrenergic receptors which suggest that, in addition to the classical postsynaptic adrenoceptors, there are also presynaptic adrenoceptors that help modulate the release of norepinephrine (NE) from peripheral as well as central noradrenergic nerve endings during nerve stimulation. In particular, stimulation of presynaptic alpha-adrenoceptors reduces this release of transmitter and the reverse is observed after blockade of these receptors. Clearcut pharmacological differences exist between the postsynaptic alpha 1-adrenoceptors that mediate the responses of certain organs and the presynaptic alpha 2-adrenoceptors that modulate the NE release during nerve stimulation. Therefore, subclassification of alpha-adrenoceptors into alpha 1 and alpha 2 subtypes is warranted but must be considered to be independent of the anatomical location of these receptors. Some noradrenergic nerve endings have also been shown to possess beta-adrenergic receptors, the stimulation of which increases the quantity of transmitter released by nerve impulses. Physiologically, these receptors could be activated by circulating epinephrine (E) and be involved in essential hypertension. A third type of catecholamine receptor found at the noradrenergic nerve ending is the inhibitory dopamine (DA) receptor, which might be of significance in the development of new antihypertensive agents. Application of these new concepts of noradrenergic neurotransmission and the subclassification of alpha-adrenoceptors to the treatment of hypertension is presented. Clonidine, for example, appears to be a potent alpha 2-adrenoceptor agonist; the central receptor involved in its antihypertensive action is pharmacologically an alpha 2-type but located postsynaptically. Clonidine also induces activation of peripheral presynaptic alpha 2-adrenoceptors, which might contribute to its cardiovascular action. The antihypertensive effects of alpha-methyldopa are related to the formation of alpha-methylnorepinephrine, a preferential alpha 2-adrenoceptor agonist, which can stimulate peripheral presynaptic alpha 2-adrenoceptors leading to a decrease of NE release and a reduction in sympathetic tone. Prazosin is a new antihypertensive agent the mechanism of action of which involves a selective blockade of postsynaptic alpha 1-adrenoceptors. This drug does not antagonize several effects of clonidine that are mediated via alpha 2-adrenoceptors. The mechanisms presently considered to account for the antihypertensive activity of beta-adrenoceptor blocking agents are numerous. It is proposed that blockade of peripheral presynaptic facilitatory beta-adrenoceptors could be of significance in the antihypertensive action of these drugs.
Hypertension
PMID:Recent developments in noradrenergic neurotransmission and its relevance to the mechanism of action of certain antihypertensive agents. 610 28

Verapamil is a calcium channel blocker widely used as an antihypertensive agent, and its pharmacological effects may partly be due to some degree of beta blockade. In order to evaluate the changes occurring in beta-2 adrenoceptor density, 40 patients with mild to moderate hypertension received verapamil 240 mg (once a day) or captopril 20 mg (twice a day) during 30 days, in a double-blind randomized study, after a placebo run-in period. The lymphocytic membrane beta-2 adrenoceptor density (Bmax) was determined before the administration of active drugs and after a 15-day treatment. After a month of treatment, most patients showed a marked reduction of their diastolic blood pressure: from 98.2 +/- 3.2 mmHg to 81.2 +/- 4.0 mmHg (p < 0.05), in the verapamil group, and from 95.0 +/- 6.0 mmHg to 82.5 +/- 4.8 mmHg (p < 0.05) in the captopril group. After 15 days of treatment, verapamil induced an up-regulation of beta-2 adrenoceptors from 39.5 +/- 8.3 fmol/mg protein to 58.5 +/- 12.0 fmol/mg protein (p < 0.05), whereas the Bmax in the captopril group did not significantly change. No significant change occurred in the two dissociation constants. This up-regulation phenomenon, common among beta-2 blockers, supports the hypothesis of verapamil's beta blockade potency.
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PMID:Is verapamil also a non-selective beta blocker? 809 51

We tested the hypothesis that genetic variation in the beta-2 adrenoceptor gene is associated with a genetic predisposition to hypertension. Offspring of two hypertensive parents were compared with offspring of two normotensive parents. The subjects were participants of the Bergen Blood Pressure Study, where couples were recruited in 1963 to 1964 and re-examined in 1990. We studied offspring of those couples in which both partners were either hypertensive or normotensive in both examinations. Twenty-three hypertensive and 22 normotensive families met the inclusion criteria. DNA samples from the first born of hypertensive family-history offspring and normotensive family-history offspring were analyzed. We used multiplex sequencing and specifically examined the promoter and the N-terminal portion of the beta-2 adrenoceptor gene. We found four genetic variants: at position -47, a C-->T substitution in the 5' leader cistron causing an Arg-->Cys exchange, at -20, a T-->C substitution, at +46 an A-->G substitution leading to an Arg16-->Gly exchange, and at +79, a C-->G substitution leading to a Gln27-->Glu exchange. The frequency of the Arg16 allele was significantly higher in the hypertensive family-history offspring compared to normotensive family-history offspring (58% vs. 28% P < 0.011). We constructed haplotypes for the four intragenic variants and found significant linkage dysequilibrium. In particular, the 5' leader cistron mutant with the wild type alleles at the other loci was significantly more frequent in offspring of hypertensive parents, compared to offspring of normotensive parents. We also performed a relative risk analysis comparing the Gly/Gly, Arg/Gly, and Arg/Arg alleles, which implicated the Arg-containing allele. Finally, we analyzed the effect of genotype on blood pressure in the offspring. We found a significant step-wise effect for all four polymorphisms examined. Our data suggest that the Arg variant of the Arg-->Gly exchange is associated with parental hypertension and higher blood pressure values in this northern European population.
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PMID:Beta-2 adrenoceptor genetic variation is associated with genetic predisposition to essential hypertension: The Bergen Blood Pressure Study. 960 74

Glucocorticoids and catecholamines exert important effects on cardiovascular physiology and metabolism. Variants of the glucocorticoid receptor gene (GRL) and the beta2-adrenergic receptor gene (ADRB2) have been associated with high blood pressure and obesity. These genes are close on human chromosome 5q31-5q32, and we undertook a linkage analysis of this region in 264 families from the general population in relation to systolic and diastolic blood pressure, body mass index, weight, height, and pulse rate. All family members were genotyped at four microsatellite loci (D5S207, D5S210, D5S519, and D5S119) located on chromosome 5q31-5q33.3. Using quantitative identity-by-descent sibling pair linkage analysis, we found that at no loci was genetic similarity associated with phenotypic similarity for systolic and diastolic blood pressure, body mass index, weight, height, or pulse rate. Although it is not possible to exclude the influence of specific combinations of certain GRL and ADRB2 polymorphisms, the absence of significant linkage in our population argues against a role for GRL or ADRB2 in physiological variation of blood pressure and body mass index.
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PMID:Linkage analysis of glucocorticoid and beta2-adrenergic receptor genes with blood pressure and body mass index. 1019 65

Recent evidence suggests that the prodownregulatory Gly16 allele of the beta-2 adrenergic receptor (beta-2 AR) is associated with essential hypertension in African Caribbeans. To further investigate the effect of the glycine (Gly)16 and arginine (Arg)16 beta-2 AR variants on hemodynamics, we investigated the agonist-mediated in vivo vasodilation in normotensive Austrian Caucasians and analyzed the results with respect to the Gly16/Arg16 polymorphism. Fifty-seven normotensive men, 20 to 32 years of age with body mass index of 18.7 to 29.9 kg/m2, were genotyped for the Arg16/Gly16 beta-2 AR alleles. All 15 Gly16/Gly16 subjects, all 12 Arg16/Arg/16 subjects, and 27 of 30 heterozygous subjects underwent hemodynamic measurements while supine after an overnight fast. The observers were unaware of the subjects' genotypes. The subjects received a graded infusion of the selective beta-2 AR agonist salbutamol (0.07, 0.14, and 0.21 microgram/kg per minute, respectively), each dose over 8 minutes. Stroke volume and blood pressure were determined continuously by means of impedance cardiography and oscillometry, respectively. The last 4 minutes of each infusion were evaluated statistically. Basal mean blood pressure was higher in the Gly16/Gly16 subjects compared with Arg16/Arg16 subjects (mean+/-SD: 81.6+/-6.14 versus 75.2+/-4.93 mm Hg, P<0.01). Homozygous Gly16 subjects showed a significantly decreased vasodilation during the first dose of salbutamol infusion compared with Arg16/Arg16 subjects (Deltatotal peripheral resistance index -17.9+/-14.4 versus -30. 6+/-8.3%, P<0.01) despite increased sympathetic counterregulation in the Arg16/Arg16 group (Deltaheart rate +16.9+/-7.0% versus +8.6+/-7. 0%, P<0.01; Deltacardiac index +39.5+/-18.5% versus 21.4+/-18.8%, P<0.05). Our results provide additional evidence that the Gly16/Arg16 alleles of the beta-2 AR are intimately related to blood pressure regulation and deserve further studies in the pathogenesis of essential hypertension.
Hypertension 1999 Jun
PMID:beta-2 Adrenergic receptor variants affect resting blood pressure and agonist-induced vasodilation in young adult Caucasians. 1037 27

Genetic variability, which influences cardiovascular phenotypes in normal persons, is likely to be relevant to cardiovascular disease. We studied normal monozygotic and dizygotic twins and found strong genetic influences on blood pressure and heart size. We then relied on the dizygotic twins and their parents to apply molecular genetic techniques. We performed a linkage analysis with markers close to the beta-2 adrenergic receptor (AR) gene locus in the dizygotic twins and their parents and found strong evidence for linkage to the quantitative traits of blood pressure and heart size. We then used allele-specific polymerase chain reaction to genotype the subjects further. We performed an association analysis and found that 4 functionally relevant polymorphisms in the beta-2 AR gene, namely Arg16/Gly, Gln27/Glu, Thr164/Ile, and a variant in the promoter region (-47C/T), were variably associated with blood pressure and heart size differences but were in linkage dysequilibrium with each other. A subsequent conditional analysis suggested that the Arg16/Gly polymorphism exerted the predominant effect. These findings underscore the importance of the beta-2 AR gene to blood pressure regulation, heart size, and probably to the development of hypertension. We suggest that a combined linkage and association approach will elucidate the genetic variability influencing blood pressure and other cardiovascular phenotypes.
Hypertension 2000 Feb
PMID:beta-2 adrenergic receptor gene variations, blood pressure, and heart size in normal twins. 1067 97


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