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

Ethnic differences in vascular adrenergic responsiveness have been implicated to be a potentially important mechanism which may be responsible for some of the variations in haemodynamic patterns between races. These differences may account for the variability in the prevalence of hypertension in different groups. The main aim of this study was to determine whether there was a difference in venous responsiveness to the vasoactive agents, phenylephrine and isoproterenol, between Mexican-Americans and White Americans. Isoproterenol is a potent non-selective beta-adrenergic agonist, phenylephrine is an alpha1-selective adrenergic agonist. Using the dorsal hand vein compliance technique, dose-response curves were constructed for the two vasoactive agents in 10 Mexican-American and 10 White American volunteers. The maximal venoconstriction for phenylephrine in the Mexican-American group was significantly less than that of the Whites in the study (71.2 +/- 20.1% vs 89.4 +/- 10.9%, P < 0.05). The log ED50 for isoproterenol in the Mexican-American group was also significantly greater than that for Whites (1.68 +/- 0.35[47.6 ng/min] vs 1.19 +/- 0.55[15.5 ng/min], P < 0.05). These results suggest that Mexican-Americans have a differential responsiveness to adrenergic vasoactive agents compared to White Americans and may be protected from the development of hypertension.
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PMID:Variability in vascular responsiveness between Mexican-Americans and White Americans. 957 66

1. Angiotensin II (AngII) and eicosanoids may be important in vascular remodelling and the pressor response via autocrine and paracrine mechanisms. We evaluated the influences of ageing and beta-adrenoceptor stimulation on the production of vascular AngII and eicosanoids in male spontaneously hypertensive rats (SHR), aged 5, 17 and 30 weeks, and age-matched Wistar-Kyoto (WKY) rats. 2. All rats were weighed and their systolic blood pressure (SBP) was measured by the tail-cuff method. Mesenteric arteries were isolated and perfused with Krebs'-Henseleit solution. The outflows of prostaglandin E2 (PGE2), 6-keto-PGF1 alpha, thromboxane B2 (TxB2) and AngII were measured by specific radioimmunoassays. 3. The SBP was higher in SHR than in WKY rats in the 17- and 30-week-old groups and increased with age. Basal levels of PGE2 were significantly lower in SHR than in WKY rats. The ratios of 6-keto-PGF1 alpha to TxB2 and PGE2 to TxB2 were significantly lower in 17-week-old SHR compared with age-matched WKY rats. Basal AngII release did not differ between SHR and WKY rats and decreased with age. Isoproterenol stimulated the release of AngII; the magnitude of the increment was greater in WKY rats than in age-matched SHR. These results show that there is an imbalance in the production of vasodilator and vasoconstrictor eicosanoids in the resistance vessels of SHR at ages at which hypertension developed. 4. This imbalance may contribute to the increased vasoconstrictor response and vascular remodelling in SHR. Our findings suggest that vascular AngII plays a role in the ageing process and that beta-adrenoceptor-stimulated release of vascular AngII is impaired in SHR.
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PMID:Production of eicosanoids and angiotensin II in resistance vessels in spontaneously hypertensive rats. 967 18

Stimulation of vascular beta-adrenoceptors leads to membrane hyperpolarization, presumably via the beta-adrenoceptor/G(s) protein/adenylate cyclase signaling cascade; the ionic mechanisms of this phenomenon remain unclear. beta-Adrenoceptor-mediated vascular relaxation is impaired with aging; however, little is known concerning whether beta-adrenoceptor-mediated hyperpolarization is altered with aging. We sought to determine the ionic mechanisms of isoproterenol-induced hyperpolarization in the rat mesenteric resistance artery, as well as the age-related changes in isoproterenol-induced hyperpolarization and their underlying mechanisms. Isoproterenol-induced hyperpolarization was inhibited by high-K(+) solution and glibenclamide (10(-6) mol/L), an inhibitor of ATP-sensitive K(+) channels (K(ATP)), but not by apamin, iberiotoxin, or charybdotoxin, inhibitors of Ca(2+)-activated K(+) channels. Isoproterenol-induced hyperpolarization was markedly less in aged rats (>/=24 months) than in adults rats (12 to 20 weeks) (3x10(-6) mol/L; -3.1 versus -9.9 mV; P<0.001; n=8 to 9). Cholera toxin (10(-9) g/mL), an activator of G(s), evoked hyperpolarization only in adult rats. Hyperpolarization to forskolin, a direct activator of adenylate cyclase, was also reduced to some extent in aged rats (10(-5) mol/L; -8.8 versus -13 mV; P<0.05; n=6), whereas hyperpolarization to levcromakalim, a K(ATP) opener, was comparable in both groups. These findings suggest that isoproterenol elicits hyperpolarization via an opening of K(ATP) in the rat resistance artery and that isoproterenol-induced hyperpolarization is attenuated in aged rats mainly because of a defective coupling of beta-adrenoceptors to adenylate cyclase and partly because of a defect at the level of adenylate cyclase, but not because of an alteration of K(ATP) per se.
Hypertension 1999 Aug
PMID:Impaired isoproterenol-induced hyperpolarization in isolated mesenteric arteries of aged rats. 1045 45

Diagnosis is central to medicine. In spite of tremendous diagnostic technological advances, no infallible test exists and in the complex diagnostic process the physician may well get lost. The ultimate feedback on the accuracy of diagnosis is the autopsy. Five patients illustrate that the autopsy may disclose unexpected results. The first patient was a 9-year-old girl who suffered from daily abdominal spasmodic pain but each time recovered. She died suddenly; autopsy revealed intestinal intussusception. A 46-year-old man who was treated for hypertension developed pain in the chest and the lower back, but there were no other signs of myocardial infarction. He died suddenly; autopsy revealed a dissecting aortic aneurysm with rupture in the left pleural cavity. A 21-year-old woman, an excellent swimmer, drowned during a swim in the sea. Autopsy revealed severe widespread coronary disease with multiple myocardial infarction. A 32-year-old Surinam woman developed acute coma and died from cardiorespiratory arrest. At autopsy she had massive pulmonary embolism and generalized lymphadenopathy due to sarcoidosis. The last patient, a 32-year-old woman suffered from fatigue after her fourth child was born. She was admitted with severe dyspnoea and her chest X-ray showed interstitial fibrosis. She died presently and autopsy revealed metastatic colon carcinoma with pulmonary lymphangitis carcinomatosa. Systematic reviews of the results of autopsies show no decline in the percentage of false diagnoses and/or unexpected findings in spite of the enormous growth of the diagnostic armamentarium. Although we may radiologically 'slice' the body in incredible detail or investigate human cells at the molecular level, the autopsy has by no means become obsolete and is an invaluable tool for quality control and teaching.
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PMID:[Truth after death]. 1059 Jul 70

beta-Adrenergic stimulation of cardiac L-type Ca(2+) channels is severely impaired in hypertrophied and failing hearts of both experimental animals and humans. The aim of this study was to test the hypothesis that chronic treatment of renovascular hypertension with captopril restores normal beta-adrenergic responsiveness of L-type Ca(2+) channels in cardiac myocytes. Left ventricular hypertrophy was induced in rabbits by unilateral renal artery banding and contralateral nephrectomy. Beginning at 3 months after banding, hypertensive rabbits were treated with captopril for 3 months. The responsiveness of L-type Ca(2+) current (I(Ca,L)) to (+/-)-isoproterenol was investigated with the whole-cell patch-clamp technique. (+/-)-Isoproterenol (1 microM) induced an increase of I(Ca,L) at 0 mV of 126 +/- 20% (n = 13) in control myocytes versus 69 +/- 11% (n = 18) in hypertrophied myocytes from rabbits 3 months after banding. The half-maximal activation concentration of (+/-)-isoproterenol was similar between control and hypertrophied myocytes. Forskolin (10 microM) induced a similar percentage of increase of I(Ca,L) in control and hypertrophied myocytes, 109 +/- 13% (n = 12) versus 120 +/- 14% (n = 11) at 0 mV. The responsiveness of I(Ca,L) to (+/-)-isoproterenol remained depressed in untreated hypertensive rabbits. (+/-)-Isoproterenol (1 microM) increased I(Ca, L) at 0 mV by 64 +/- 8% (n = 14) in myocytes isolated from rabbits 6 months after banding versus 111 +/- 15% (n = 16) in age-matched controls. In captopril-treated rabbits, 1 microM (+/-)-isoproterenol increased I(Ca,L) by 110 +/- 11% (n = 17). We conclude that the maximal response of I(Ca,L) to (+/-)-isoproterenol was severely depressed in hypertrophied myocytes. Chronic treatment of renovascular hypertension with captopril can restore normal responsiveness of I(Ca,L) to (+/-)-isoproterenol in cardiac myocytes.
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PMID:Effects of captopril treatment of renovascular hypertension on beta-adrenergic modulation of L-type Ca(2+) current. 1060 48

A 50-yaer-old man with hypertension had been treated for supraventricular tachycardia with several medications for nine years. In 1990, he was started on amiodarone but a year later he developed side effects causing discontinuation of amiodarone. Because of his recurrent episodes of palpitations associated with near syncope, chest pain and shortness of breath, he underwent an electrophysiology study in 1992 that showed orthodromic AVRT with the presence of a concealed left-sided accessory bypass tract. Scheduled for radiofrequency ablation the following day, after catheters were placed and during mapping of the lateralmitral annulus, his tachycardia stopped abruptly without further inducability. Isoproterenol infusion during atrial and ventricular stimulation also failed to induce his original tachycardia. A year later, the patient presented with palpitations that felt different than his previous experiences. Work-up at that point only revealed a parasystolic focus on a 24-hour ECG monitoring without any form of supraventricular tachycardia. This represents a very unusual case by which the left lateral accessory pathway was mechanically ablated with catheter manipulation. This led to the disappearance of the orthodromic tachycardia that was easily induced before due to the activity of his parasytolic focus. The latter continued for the following four years but the patient has had no recurrences of his tachycardia.
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PMID:Mechanical Ablation of Concealed Left Lateral Bypass Tract. 1068 61

Inotropic responsiveness to beta-adrenergic stimulation is generally found to be impaired in left ventricular (LV) hypertrophy and failure. To investigate the mechanisms by which angiotensin-converting enzyme inhibitor therapy may modulate inotropic responsiveness with long-term pressure overload, we studied the effects of captopril treatment on cardiac gene expression, LV muscle mechanical contraction, and intracellular calcium (Ca(2+)) transients from spontaneously hypertensive rats (SHR). LV papillary muscles from untreated SHR, age-matched normotensive Wistar-Kyoto rats (WKY), and SHR treated with captopril (CAP(Rx) started at 12, 18, and 21 months of age) were studied. All animals were studied at 24 months of age or when heart failure developed. In untreated SHR, alpha-myosin heavy chain (MHC) gene expression and protein were decreased, the Ca(2+) transient (with the bioluminescent indicator aequorin) was prolonged, and abundance of Na(+)/Ca(2+) exchanger mRNA levels increased in comparison to WKY. Active stress development at L(max) and the maximum rate of stress development were depressed and contractile duration prolonged in SHR relative to WKY. Isoproterenol administration further decreased active stress in untreated SHR despite an increase in intracellular Ca(2+) levels. In CAP(Rx) SHR, alpha-MHC gene expression and protein levels were increased, the Ca(2+) transient was not prolonged, Na(+)/Ca(2+) exchanger expression was downregulated, and papillary muscle function demonstrated increased active stress and maximum rate of stress development in response to isoproterenol. The increased abundance of alpha-MHC mRNA in conjunction with an increase in V(1) myosin isozyme suggests that captopril affects transcriptional regulation of cardiac gene expression. Restored LV inotropic responsiveness to beta-adrenergic stimulation in CAP(Rx) SHR appears to be coupled to normalization of Na(+)/Ca(2+) exchanger mRNA expression, upregulation of V(1) myosin isozyme levels, and increased speed of contraction.
Hypertension 2000 Jun
PMID:Altered inotropic responsiveness and gene expression of hypertrophied myocardium with captopril. 1085 64

A 21-year-old woman with hypertension confirmed on ambulatory blood pressure monitoring and unresponsive to beta-blockers, diltiazem and amiloride was found to have serum potassium, renin and aldosterone levels at or just below the lower end of normal. Urinary glucocorticoid metabolite analysis revealed high excretion of cortisol and androgen metabolites, with normal serum cortisol levels. This pattern suggests a partial glucocorticoid resistance syndrome; such patients are more responsive to ACE inhibitors and spironolactone.
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PMID:Increased urinary cortisol and androgen metabolites in a young female with hypertension: partial glucocorticoid resistance syndrome. 1089 20

1. The aim of the present work was to study the possible modulatory role of nitric oxide (NO) on the positive inotropic effect induced by the beta-adrenoceptor agonist isoprenaline in myocardial contractility, and whether this modulation is altered by hypertension. 2. The study was performed using right ventricular strips from the hearts of 6-month-old male Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHR). The contractile force of electrically-stimulated ventricular strips was measured by a force-displacement transducer. 3. Isoprenaline (from 10 nmol l(-1) to 10 micromol l(-1)) induced a concentration-dependent increase in cardiac contractility in strips from both rat strains. This positive inotropic effect to isoprenaline was reduced by the NO donor sodium nitroprusside (SNP, 0.1 mmol l(-1)) in muscles from WKY rats and slightly increased in those from SHR. The SNP-induced increase in strips from SHR was abolished by superoxide dismutase (100 U ml(-1)). 4. N(G)-nitro-arginine-methyl ester (L-NAME, 0.1 mmol l(-1)) and 1H-[1,2,4]oxadiazolo[4,3]-quinoxalin-1-one (ODQ, 10 micromol l(-1)), respective inhibitors of NO synthase and guanylate cyclase, increased the response to isoprenaline in muscles from WKY rats, whereas it was unaltered in strips from SHR. 5. In strips from WKY rats, the combination of ODQ and SNP produced an increase in the response elicited by isoprenaline, which was similar to that observed with ODQ or L-NAME. 8-Br-cyclicGMP (8-Br-cGMP, 0.1 mmol l(-1)), a permeable and structural cGMP analogue, decreased the effect induced by isoprenaline only in muscles from WKY rats. 6. These results suggest that the positive inotropic response to isoprenaline in ventricular strips from WKY rats is negatively modulated by NO, and positively by superoxide anions in those from SHR. The lack of a modulatory response to NO in ventricular strips from SHR is probably a result of an alteration of mechanisms in NO-signalling pathway downstream of cGMP formation in SHR hearts.
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PMID:Different sensitivity of isoprenaline-induced responses in ventricular muscle to sodium nitroprusside in normotensive and spontaneously hypertensive rats. 1109 46

Stimulation of beta-adrenoceptors leads to vascular smooth muscle hyperpolarization, presumably through the beta-adrenoceptors/Gs protein/adenylate cyclase/ATP-sensitive K(+)-channels (KATP) signaling cascade, which may play an important role in the sympathetic control of membrane potential. beta-Adrenoceptor-mediated hyperpolarization has been shown to be impaired in the established stage of experimental hypertension. The present study tested the hypothesis that beta-adrenergic hyperpolarization may be defective before the development of hypertension in some forms of genetic hypertension. We evaluated beta-adrenoceptor-mediated hyperpolarization using microelectrodes in mesenteric resistance arteries from 5-week-old, prehypertensive, spontaneously hypertensive rats (SHR) and age-matched Wistar-Kyoto rats (WKY). Isoproterenol-induced hyperpolarization was significantly smaller in SHR than in WKY (10(-7) mol/L: -4.6+/-0.6 versus -7.8+/-0.8 mV, P<0.01; 10(-6) mol/L -7.8+/-0.5 versus -9.8+/-0.6 mV, P<0.05; n=9). Furthermore, hyperpolarization to cholera toxin, a direct activator of Gs protein, was also impaired in SHR. On the other hand, hyperpolarization to forskolin, an adenylate cyclase activator, and to levcromakalim, a KATP opener, was comparable between groups. These findings suggest that beta-adrenoceptor-mediated hyperpolarization is defective in SHR before the development of hypertension, presumably because of an abnormality at the Gs protein site. Considering the importance of membrane potential in the control of vascular tone, altered beta-adrenergic control of membrane potential might play a role in the development of hypertension in SHR.
Hypertension 2001 Feb
PMID:Impaired beta-adrenergic hyperpolarization in arteries from prehypertensive spontaneously hypertensive rats. 1123 Mar 43


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