bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of beta-adrenergic receptor blockade on atrial natriuretic peptide in essential hypertension.
Authors: Nakaoka H , Kitahara Y , Amano M , Imataka K , Fujii J , Ishibashi M , Yamaji T
Published: June 2012

Plasma levels of atrial natriuretic peptide (ANP) were measured in 32 untreated subjects with essential hypertension and in 31 patients undergoing long-term treatment with beta-blockers. Patients receiving beta-blockers had significantly higher mean plasma ANP levels (72.0 +/- 36.0 [SD] pg/ml) than did untreated hypertensive subjects (39.8 +/- 15.8 pg/ml; p less than 0.01) and healthy normotensive controls (33.9 +/- 16.6 pg/ml; n = 61, p less than 0.01), while the mean plasma ANP concentration in untreated hypertensive subjects was not statistically different from that in control subjects. Administration of atenolol, 50 mg/day, for 4 weeks to 10 untreated subjects resulted in a significant (p less than 0.001) rise in plasma ANP levels (from 38.8 +/- 9.5 to 68.7 +/- 20.6 pg/ml). In 31 patients undergoing long-term treatment with beta-blockers, multivariate regression analysis revealed that age, pretreatment mean blood pressure, and plasma concentration of cyclic 3',5'-guanosine monophosphate (cGMP) were significant predictors of plasma ANP levels. These results suggest that beta-adrenergic receptor blockade in patients with essential hypertension elevates plasma ANP levels with a concomitant rise in cGMP concentrations, and that increased ANP in plasma may play a role in the compensatory mechanism that operates in response to beta-adrenergic receptor blockade.
Erythrocyte ghost Na+,K+-ATPase and blood pressure.
Authors: Rygielski D , Reddi A , Kuriyama S , Lasker N , Aviv A
Published: June 2012

To examine the relationship between body mass index, blood pressure, and the Na+,K+-adenosine triphosphatase (ATPase) system, we measured the erythrocyte ghost Na+,K+-ATPase and the erythrocyte Na+ concentration in 120 blacks and 127 whites (136 males and 111 females). Blacks showed a 13.9% higher erythrocyte Na+ (7.63 +/- 0.19 vs 6.70 +/- 0.11 [SEM] mEq/L; p = 0.0001) and a 16.1% lower erythrocyte ghost Na+,K+-ATPase activity (140.3 +/- 4.2 vs 167.3 +/- 4.7 nmol inorganic phosphate/mg protein/hr; p = 0.0002) than whites. Male subjects demonstrated a 6.4% higher erythrocyte Na+ (7.35 +/- 0.17 vs 6.91 +/- 0.14 mEq/L; p = 0.043) and an 11.5% lower Na+,K+-ATPase activity (145.7 +/- 3.7 vs 164.7 +/- 5.5 nmol inorganic phosphate/mg protein/hr; p = 0.0015) than female subjects. Significant (p less than 0.001) negative correlations were identified for the systolic, diastolic, and mean blood pressure levels and the erythrocyte ghost Na+,K+-ATPase. These findings were complemented by positive correlations for the blood pressure levels and erythrocyte Na+ concentrations. The body mass index was negatively correlated with erythrocyte ghost Na+,K+-ATPase and it accounted for 6.7%, 5.6%, and 6.1% of the variabilities in the systolic, diastolic, and mean blood pressure levels, respectively. Variabilities of 1.4% systolic, 12.3% diastolic, and 11.1% in mean arterial pressure were attributable to the erythrocyte ghost Na+,K+-ATPase activity. Provided that findings in erythrocytes also reflect the relative status of the vascular smooth muscle cell Na+,K+-ATPase, the predisposition of black, male, and obese persons to hypertension may relate, among other factors, to a lower activity of this enzyme system, which results in an increased vascular tone.
Predictive value of exercise renography for presurgical evaluation of nephrogenic hypertension.
Authors: Clorius J H , Allenberg J , Hupp T , Strauss L G , Schmidlin P , Irngartinger G , Wagner R , Mukhopadhyay C
Published: June 2012

Functional omicron-iodohippurate scintigrams were obtained in 18 hypertensive patients. Each patient was examined in the prone position and during exercise. An exercise-induced transient, bilateral, hippurate transport disturbance was sought as an expression of an exercise-mediated cortical perfusion abnormality. The study sought to test the hypothesis that patients who present evidence for an exercise-induced renal perfusion disturbance would have stabilized hypertension that was no longer surgically curable because of morphological changes of the peripheral vasculature. All 18 patients continued on to therapy: 13 proceeded to renovascular reconstructive surgery, 2 had a unilateral nephrectomy, and 3 were treated with percutaneous transluminal renal angioplasty. During preoperative exercise renography, evidence of bilateral renal dysfunction developed in 10 of 18 hypertensive patients during ergometric stress (abnormal exercise response). Following surgical therapy nine of these patients with abnormal exercise scintigrams continued to have hypertensive disease, while one patient was cured. The exercise renograms of eight hypertensive patients were not influenced by the exercise protocol, and operation cured seven of these eight patients. The results suggest that an accentuated vascular response to exercise occurs in the maintenance phase of renovascular hypertension, a disturbance not observed while the hypertension is curable by surgical therapy.
Aspirin enhances the antihypertensive effect of captopril in spontaneously hypertensive rats.
Authors: Quilley C P , Chiba S , Quilley J , McGiff J C
Published: June 2012

Activation of renal or vascular prostaglandin mechanisms (or both) has been proposed to contribute to the antihypertensive action of captopril. In conscious spontaneously hypertensive rats (SHR) studied in the established phase of hypertension, the blood pressure-lowering effect of captopril, 30 mg/kg/12 hr p.o. given for 7 days, was greatly enhanced by the addition of aspirin, 200 mg/kg/day s.c. Systolic blood pressure decreased from 185 +/- 6 and 182 +/- 4 to 135 +/- 3 mm Hg in rats treated, respectively, with captopril and aspirin or captopril alone, and was unaltered by either vehicle or aspirin alone. Water intake was inconsistently affected by captopril but was increased (p less than 0.01) by aspirin and was even higher after captopril-aspirin treatment (p less than 0.01). Urine volume was elevated in all 3 drug-treated groups, increasing threefold after captopril-aspirin treatment. Excretion of sodium and potassium was unchanged by any treatment regimen. In the vehicle group, prostaglandin F2 alpha excretion, measured by radioimmunoassay, ranged between 65 and 93 ng/8 hr and was twofold to fourfold higher than that of prostaglandin E2. Prostaglandin F2 alpha was unaffected during captopril treatment, whereas prostaglandin E2 excretion decreased to 12 +/- 2 ng/8 hr (p less than 0.01) by Day 7. Long-term aspirin treatment, either with or without captopril, did not cause sustained inhibition of renal prostaglandin excretion, although a transient effect occurred within the first four hours of administration. These results indicate 1) aspirin potentiates the blood pressure-lowering effect of captopril in SHR, an effect that is associated with a threefold increase in urine flow.(ABSTRACT TRUNCATED AT 250 WORDS)
Spontaneously hypertensive rats exhibit reduced hypothalamic noradrenergic input after NaCl loading.
Authors: Wyss J M , Chen Y F , Jin H , Gist R , Oparil S
Published: June 2012

Spontaneously hypertensive rats (SHR) of the Okamoto strain exhibit a significant exacerbation in severity of hypertension when fed diets high in NaCl. To examine the hypothesis that abnormalities in the monoaminergic innervation of the hypothalamus and brainstem contribute to the NaCl-induced exacerbation of hypertension, the monoamine and monoamine metabolite contents of specific hypothalamic and brainstem regions thought to be involved in the pathogenesis of hypertension were determined in SHR fed a diet containing 8% or 1% NaCl for either 2 or 6 weeks beginning at age 8 weeks. SHR maintained on the 8% NaCl diet for 2 weeks displayed significant decreases in norepinephrine in both the anterior and posterior hypothalamic regions but not in other brainstem or hypothalamic regions, as compared with animals consuming 1% NaCl. In addition, stores of the principal terminal norepinephrine metabolite 3-methoxy-4-hydroxyphenylglycol were reduced in the anterior hypothalamic region of SHR fed an 8% NaCl diet for 2 weeks. After 6 weeks on the diets, SHR fed 8% NaCl showed small but statistically nonsignificant reductions in norepinephrine stores of the anterior hypothalamic region as compared with SHR fed a basal diet, while WKY fed 8% NaCl had significantly elevated norepinephrine stores in the anterior hypothalamic region as compared with WKY fed a basal diet. There was a significant group X diet interaction (p less than 0.05). After 6 weeks on the 8% NaCl diet, SHR (but not WKY) displayed a significant reduction in norepinephrine content of the posterior hypothalamic region. No NaCl-induced differences in norepinephrine stores were found in the pons or medulla of either strain.(ABSTRACT TRUNCATED AT 250 WORDS)
Echocardiographic left ventricular mass and function in the hypertensive baboon.
Authors: Crawford M H , Walsh R A , Cragg D , Freeman G L , Miller J
Published: June 2012

Nonhuman primates with chronic systemic hypertension provide an ideal model for studying structural and functional alterations associated with compensatory cardiac hypertrophy. Since noninvasive techniques are useful for the longitudinal evaluation of these animals, we sought to critically asses the M-mode echocardiographic estimation of left ventricular mass in the baboon and to characterize estimates of left ventricular size and function in baboons with chronic renal hypertension. In 23 baboons (12 normotensive, 11 chronic hypertensive), M-mode echocardiography-determined left ventricular mass was 73 +/- 13 (SE) g as compared with the necropsy weight of 69 +/- 11 g (p = NS), and the correlation was excellent (r = 0.94). When 30 chronically hypertensive baboons being observed longitudinally were compared with 10 normotensive control animals studied under identical conditions, several differences were noted in measures derived from echocardiography and high fidelity pressure measurements. Left ventricular systolic pressure was considerably higher in the hypertensive baboons (113 +/- 23 vs 90 +/- 11 mm Hg; p less than 0.001), as was left ventricular mass (148 +/- 60 vs 103 +/- 38 g; p less than 0.03). However, since the ratio of posterior wall thickness to cavity dimension was larger in the hypertensive baboons (0.52 +/- 0.17 vs 0.43 +/- 0.07; p less than 0.05), this concentric hypertrophy maintained values for left ventricular meridional stress at the same level as in the control animals. Despite matched heart rate and left ventricular stress, the rates of change in left ventricular dimensions and wall thickness in systole and diastole were all approximately 25% less in the hypertrophied baboons.(ABSTRACT TRUNCATED AT 250 WORDS)
Assessment of the permeability of the blood-retinal barrier in hypertensive rats.
Authors: Lightman S , Rechthand E , Latker C , Palestine A , Rapoport S
Published: June 2012

We assessed the permeability surface area products at the blood-retinal barrier and blood-brain barrier to sucrose (molecular weight, 340) and microperoxidase (molecular weight, 2000) following acute hypertension induced by metaraminol in Wistar-Kyoto rats (controls) and during chronic hypertension in spontaneously hypertensive rats. In acute hypertension, the permeability surface area product for sucrose was increased at the blood-retinal barrier and at the blood-brain barrier over control values (p less than 0.02), and the vessels became leaky to microperoxidase. In chronic hypertension, the permeability of the blood-retinal barrier to sucrose was increased over that in control animals (p less than 0.02), whereas the permeability of the blood-brain barrier was unaffected. Neither barrier leaked microperoxidase. These results indicate that the blood-brain barrier and the blood-retinal barrier are similarly affected in acute hypertension and that in chronic hypertension, the blood-brain barrier is unaffected whereas the blood-retinal barrier is rendered more permeable to small, but not large, solutes.
Improved myocardial efficiency in the working perfused heart of the spontaneously hypertensive rat.
Authors: Tubau J F , Wikman-Coffelt J , Massie B M , Sievers R , Parmley W W
Published: June 2012

We assessed the relationship between determinants of myocardial oxygen demand--wall stress, peak rate of change of pressure and heart rate--and measured myocardial oxygen consumption over a range of loading conditions in the perfused, working heart of 6-month-old spontaneously hypertensive rats (SHR) and control Wistar-Kyoto rats (WKY). Two isolated heart preparations, an aortic-ejecting heart and an isovolumically contracting preparation with and without isoproterenol (10(-7)M) added, were employed. Under a constant perfusion pressure of 110 mm Hg, the heart rate, developed wall stress, and peak rate of change of pressure were not different between the two groups, but coronary flow and myocardial oxygen consumption were significantly lower in the SHR. Systolic values of myocardial high energy phosphate compounds (adenosine 5'-triphosphate, phosphocreatine) and myocardial lactate in the two preparations were not significantly different between SHR and WKY. Following adenosine infusion at maximum developed pressure (isovolumic preparation), both SHR and WKY demonstrated preservation of coronary reserve. These results indicate that cardiac hypertrophy represents a compensatory adaptation with improved mechanical efficiency in the 6-month-old SHR when maximally stressed and may be related to the shift from V1 to V2 and V3 isomyosin phenotypes that was observed in the hypertensive animals.
Association of haptoglobin with sodium sensitivity and resistance of blood pressure.
Authors: Weinberger M H , Miller J Z , Fineberg N S , Luft F C , Grim C E , Christian J C
Published: June 2012

Sodium sensitivity and resistance of blood pressure were examined in 117 normotensive and 85 hypertensive subjects by means of a protocol using rapid extracellular fluid volume expansion with intravenously administered saline (2 L over 4 hours) followed by a day of low dietary sodium intake (10 mEq) and volume contraction induced by a diuretic (furosemide, 120 mg orally). Genetic markers were also examined. Both hypertensive and normotensive subjects with haptoglobin 1-1 phenotype were significantly more (p less than 0.05) likely to be sodium-sensitive than were those with 2-1 or 2-2 phenotypes, and subjects with 2-2 phenotypes were more apt to be sodium-resistant. A second population was examined in which both adults and children with haptoglobin 1-1 phenotype were found to have significantly (p less than 0.05) higher casual systolic and diastolic blood pressures. These two studies independently confirm a relationship between haptoglobin phenotypes and blood pressure and suggest an environmental factor (sodium) as well.
Selective modification of renal alpha 2-adrenergic receptors in Milan hypertensive rat strain.
Authors: Parini A , Diop L , Ferrari P , Bondiolotti G P , Dausse J P , Bianchi G
Published: June 2012

Cerebral and renal alpha-adrenergic receptors play an important role in the control of blood pressure. We studied alpha-adrenergic receptors in the cerebral and renal cortex of Milan hypertensive strain (MHS) and normotensive strain (MNS) rats, a genetic model of spontaneous hypertension linked to a kidney abnormality. Binding of the selective alpha 1-adrenergic antagonist [3H]prazosin and the alpha 2-adrenergic antagonist [3H]rauwolscine was used for receptor studies in tissues of prehypertensive (24-day-old) and hypertensive (60-day-old) rats. In the cerebral cortex, no between-strain differences in alpha 1-adrenergic and alpha 2-adrenergic receptor density and affinity were observed in prehypertensive and hypertensive periods. The density of these receptors increased similarly with age in MHS and MNS rats. In the renal cortex, the differences between MHS and MNS rats concerned alpha 2-adrenergic receptors only. Compared with their age-matched normotensive controls, MHS rats showed 1) a lower affinity for the antagonist (p less than 0.05) in the prehypertensive period, 2) absence of the normal age-related increase in receptor density, and 3) a lower density of [3H]rauwolscine binding sites (p less than 0.001) in the hypertensive period. In this period, studies of competitive inhibition of [3H]rauwolscine binding showed that l-epinephrine bound to one class of sites in MHS rats (pseudo-Hill plot, 0.90) and to two classes in MNS rats (pseudo-Hill plot, 0.68). In addition, the lack of any guanylylimidodiphosphate effect on the l-epinephrine competition curve observed in MHS rats suggests the uncoupling of these receptors from the guanosine 5'-triphosphate binding protein.(ABSTRACT TRUNCATED AT 250 WORDS)
A gamma-melanocyte stimulating hormone-like peptide causes reflex natriuresis after acute unilateral nephrectomy.
Authors: Lin S Y , Chaves C , Wiedemann E , Humphreys M H
Published: June 2012

Previous studies have shown that acute unilateral nephrectomy stimulates sodium (UNaV) and potassium (UKV) excretion by the remaining kidney through reflex pathways requiring an intact pituitary gland, and the natriuresis is accompanied by an increase in the plasma concentration of a peptide or peptides derived from the adrenocorticotropic hormone-beta-endorphin precursor molecule pro-opiomelanocortin. We tested the hypothesis that gamma-melanocyte stimulating hormone (gamma-MSH) was such a peptide involved in the postnephrectomy natriuresis. In six rats undergoing sham nephrectomy, no change in UNaV or UKV occurred and plasma immunoreactive gamma-MSH-like material was 40 +/- 18 (SD) fmol/ml 2 hours after the sham procedure. In 10 rats undergoing acute unilateral nephrectomy, UNaV and UKV from the remaining kidney increased significantly, and immunoreactive gamma-MSH was 81 +/- 36 fmol/ml (p less than 0.02). In individual studies, the increase in UNaV after nephrectomy correlated with the postnephrectomy concentration of immunoreactive gamma-MSH (r = 0.75, p less than 0.001). In 17 rats injected with serum or globulin from control rabbits, unilateral nephrectomy led to the expected increases in UNaV and UKV. In 23 rats injected with serum or globulin from rabbits immunized against gamma-MSH, no postnephrectomy natriuresis occurred and the kaliuresis was blunted. In hydropenic, mineralocorticoid-treated rats, intravenous infusion of synthetic gamma-MSH led to natriuresis and kaliuresis with no change in inulin clearance; pretreatment with rabbit anti-gamma-MSH antiserum blocked this effect of peptide infusion.(ABSTRACT TRUNCATED AT 250 WORDS)
Enhanced phospholipase C activity in the vascular wall of spontaneously hypertensive rats.
Authors: Uehara Y , Ishii M , Ishimitsu T , Sugimoto T
Published: June 2012

To explore the roles of vascular phospholipase C activity in the development of hypertension, phospholipase C activity was examined in the aortic wall of spontaneously hypertensive rats (SHR). Phospholipase C activity was significantly enhanced (+87%, p less than 0.005) in 14-week-old SHR as compared with normotensive Wistar-Kyoto rats (WKY). The enzymatic activities were positively correlated with the levels of blood pressure in both of the rat strains (r = 0.62, p less than 0.003). Vascular phospholipase C was also significantly activated (+62%; p less than 0.006) in the aortic wall of 4-week-old prehypertensive SHR, as compared with age-matched WKY. In contrast, vascular phospholipase A2 activity was unaffected in the aortic wall of either adult or very young SHR. There was no difference in the cardiac phospholipase C activity between adult SHR and WKY. The vascular phospholipase C of SHR had a lower Michaelis constant (Km) value than that of WKY. Moreover, its pH profile and calcium requirement differed in part from those of WKY. These results indicate that the activation of vascular phospholipase C precedes the development of hypertension and that the enhancement may be induced by both quantitative and qualitative changes in phospholipase C in SHR.
Effects of thyroid function on blood pressure. Recognition of hypothyroid hypertension.
Authors: Streeten D H , Anderson G H , Howland T , Chiang R , Smulyan H
Published: June 2012

Hypothyroidism has been known to be associated, at times, with diastolic hypertension. We have found in 40 thyrotoxic patients that the induction of hypothyroidism by radioiodine therapy significantly increased diastolic blood pressure, raising it above 90 mm Hg in 16 (40%) of the patients. Restoration of euthyroidism with thyroxine administration significantly reduced the systolic and diastolic blood pressures in these patients, with a fall in diastolic pressure below 90 mm Hg in nine of 16 patients. The prevalence of hypothyroidism was determined by measurements of serum thyroxine and thyrotropin concentrations in 688 consecutive hypertensive patients, referred for evaluation and therapy of their hypertension. Hypothyroidism was found in 25 (3.6%) of the patients. Restoration of normal serum thyroxine and thyrotropin levels with thyroid hormone replacement therapy lowered diastolic blood pressure to levels below 90 mm Hg in 32% of these patients who could be followed up after withdrawal of all antihypertensive drug therapy when euthyroidism had been restored (i.e., 1.2% of the 688 patients). It is concluded that diastolic hypertension resulting from hypothyroidism is a relatively common disorder, present in 1.2% of our referred hypertensive patients, that should be sought and treated.
Crossover design to test antihypertensive drugs with self-recorded blood pressure.
Authors: Ménard J , Serrurier D , Bautier P , Plouin P F , Corvol P
Published: June 2012

In a double-blind, within-patient study, blood pressure was measured at regular intervals at the clinic by the physician and each day at home by the patient. Both methods of blood pressure measurement demonstrated an antihypertensive effect of the diuretics chlorthalidone (25 mg) and triamterene (50 mg) and the beta-blocker oxprenolol (160 mg) and the greater efficacy of the combination of the two therapies. During placebo, as well as during active treatment, blood pressure values were higher at the clinic than at home, except when the patients were taking the beta-blocker, which minimized the arousal response during blood pressure measurements in the clinic. With 2-week treatment periods, separated by 2 weeks of placebo administration, blood pressure returned toward its initial level after each of the three treatments and none of the carryover effects was significant at the 5% level. This methodology was intended to make it possible to demonstrate in 27 patients at the clinic and in 20 patients with measurements made at home, at the usual statistical risks (alpha = 5%, beta = 10%), a fall of 5 mm Hg in diastolic blood pressure in comparison with a placebo. Moreover, at the end of this 3-month follow-up, each patient could continue to receive the treatment that was the most effective and the best tolerated. In conclusion, the use of a within-patient trial design, with a 15-day washout period between active treatments and careful recording of blood pressure values, can minimize the number of patients included in hypertension trials and offer to each patient the possibility of individualization of treatment.
Individual responses to converting enzyme inhibitors and calcium antagonists.
Authors: Bidiville J , Nussberger J , Waeber G , Porchet M , Waeber B , Brunner H R
Published: June 2012

This study was designed to assess whether the acute blood pressure response of an individual hypertensive patient to a calcium antagonist or an angiotensin converting enzyme (ACE) inhibitor is a good predictor of the long-term efficacy of these drug classes in this particular patient. The concept that good responses to ACE inhibitors and calcium antagonists may be mutually exclusive was also tested. Sixteen patients were included in a randomized crossover trial of enalapril, 20 mg daily, and diltiazem, 120 mg daily, for 6 weeks each. Blood pressure was measured by ambulatory blood pressure recording. During the washout phase, the acute effect of nifedipine, 10 mg p.o., and enalaprilat, 5 mg i.v., was evaluated. Nifedipine and enalaprilat reduced blood pressure equally well. The long-term blood pressure reduction induced by enalapril and diltiazem was similar. The acute blood pressure response to a given drug was not a good predictor of the result obtained with long-term therapy. No age dependency of the antihypertensive effect of either drug class was apparent. There was no evidence that a good response to one drug excluded a similarly good response to the other.
Effects of atrial natriuretic factor and vasopressin on cyclic nucleotides in cultured kidney cells.
Authors: Náray-Fejes-Tóth A , Carretero O A , Fejes-Tóth G
Published: June 2012

The cellular mechanism of the action of atrial natriuretic factor (ANF) is thought to involve activation of guanylate cyclase. Increasing evidence shows a direct tubular effect of ANF. Part of the ANF-induced diuresis has been suggested to be due to inhibition of the action of arginine vasopressin (AVP) in the cortical collecting tubule. In this study we investigated the effect of ANF on cyclic nucleotide production in primary cultures of cortical collecting tubule cells immunodissected with a monoclonal antibody. ANF caused a dose-dependent stimulation in cyclic guanosine 3',5'-monophosphate (cGMP) production; the half-maximal stimulation was observed at approximately 1 nM of ANF. ANF (0.01-100 nM) had no effect on cyclic adenosine 3',5'-monophosphate (cAMP) accumulation in cortical collecting tubule cultures. AVP caused a dose-dependent increase in cAMP production, and this effect was not altered by the simultaneous addition of ANF (100 nM). Similarly, ANF-induced cGMP stimulation was not influenced by AVP (10 nM). We conclude that 1) ANF has a direct stimulatory action on cGMP production by cultured cortical collecting tubule cells and 2) any interaction between ANF and AVP is likely to occur at steps distal to cyclic nucleotide formation.
Pressor mechanisms linked obligatorily to spontaneous hypertension in the rat.
Authors: Mills E , Bruckert J W
Published: June 2012

To identify genetic factors linked obligatorily to hypertension in the rat, pithed spontaneously hypertensive rats (SHR) were compared with genetically similar (Wistar-Kyoto rats; WKY) and different (Sprague-Dawley) normotensive strains. The only variables that distinguished SHR from both WKY and Sprague-Dawley rats were a greater maximum pressor response to electrical stimulation of sympathetic outflow and decreased sensitivity to submaximal doses of the alpha 1-adrenergic agonist methoxamine (i.e., higher ED50). SHR had in common with Sprague-Dawley rats basal blood pressure after pithing plus adrenalectomy and the maximum pressor response to methoxamine; both these values were higher than those in WKY. All strains demonstrated equal sensitivity of the vasoconstrictor response to endogenous norepinephrine released by electrical simulation at submaximal frequency, even though sensitivity to the alpha 1-adrenergic receptor agonist was lower in SHR. The alpha 2-adrenergic receptor antagonist rauwolscine attenuated the pressor response to electrical stimulation in SHR and WKY but increased it in Sprague-Dawley rats. The alpha 1-adrenergic receptor antagonist prazosin attenuated the response more in SHR and WKY than in Sprague-Dawley rats. We conclude that 1) sympathetic hyperactivity is linked obligatorily to hypertension in SHR; 2) increased basal blood pressure and noradrenergic vasoconstrictor response are present in SHR, but they are not obligatorily linked to hypertension; 3) feedback inhibition of norepinephrine release is comparable in SHR or WKY and poorly developed compared with that in Sprague-Dawley rats; 4) decreased sensitivity of the pressor response to stimulation of vascular alpha 1-adrenergic receptors in SHR compensates partially for increased sympathetic activity or hyperinnervation, or both.
Partially endothelium-dependent vasodilator effect of adenosine in rat aorta.
Authors: Yen M H , Wu C C , Chiou W F
Published: June 2012

The vasodilator effect of adenosine on the contraction induced by phenylephrine, an alpha 1-adrenergic receptor agonist, was investigated in the isolated rat aorta. We found that the effect of adenosine was greater in intact aortas than in endothelium-denuded preparations. Denuding caused a parallel shift of the dose-response curve of adenosine to the right by a factor of five in comparison with intact aorta. This finding indicates that the relaxing effect of adenosine is partially endothelium-dependent in rat aorta. The mechanism of action of adenosine on vascular smooth muscle was also investigated in receptor-mediated and voltage-dependent calcium influx experiments performed with the addition of phenylephrine and high potassium concentrations, respectively. Although adenosine significantly inhibited only the tonic phase of the contraction induced by phenylephrine (10(-5) M), it did so to both the fast and slow phases of the contraction produced by high potassium concentrations (75 mM) with no preferential difference. In comparison to verapamil, a calcium entry blocker, adenosine behaved in a manner similar to that of verapamil in counteracting the constriction induced by either phenylephrine or potassium. We conclude that the vasodilator effect of adenosine is partially endothelium-dependent and that the mechanism of this effect may involve the inhibition of calcium influx and the release of an endothelium-derived relaxing factor.
Sexual dysfunction in hypertensive men. A critical review of the literature.
Authors: Bansal S
Published: June 2012

Sexual dysfunction is common in hypertensive men and often is first reported by patients while receiving hypotensive therapy, leading to a widespread belief by patients and physicians that the sexual dysfunction is caused by a specific antihypertensive medication. However, it is unclear from the literature whether this problem is related to hypertension or to its therapy. Further, whether the erectile failures reported during therapy are a result of 1) reduced penile blood flow secondary to reduction of blood pressure after antihypertensive treatment or to obstructive vascular disease (or both) or 2) specific drug effects has not been well studied. Because of these unresolved issues, this common problem is not well managed and contributes to noncompliance with therapy by hypertensive male patients, which impedes the attainment of satisfactory blood pressure control. The present article reviews the literature related to hypertension and sexual function in men and outlines a management strategy for clinicians that attempts to document normalcy of sexual function before initiating treatment in newly diagnosed hypertensive patients. Further, it does not ascribe causality to specific antihypertensive agents for the sexual dysfunction reported by treated hypertensive patients but attempts instead to delineate the pathogenesis of the dysfunction. Once the pathogenesis is established, treatment plans can be implemented to restore normotension and maintain adequate sexual function among treated hypertensive men. The article also discusses how applied research in this area may be performed.
Cellular hypertrophy in mesenteric resistance vessels from renal hypertensive rats.
Authors: Korsgaard N , Mulvany M J
Published: June 2012

To determine whether the increased thickness seen in media of mesenteric resistance vessels of Wistar-Kyoto rats made hypertensive by a Goldblatt procedure (one-kidney, one clip model) was due to hypertrophy or hyperplasia of smooth muscle cells, the cellular dimensions of these vessels were estimated using a new, unbiased stereological method (the disector). Furthermore, to investigate whether the changes seen could be secondary to the increased blood pressure, morphometric measurements were also made in renal arcuate arteries, which, due to the constricting silver clip, probably had not been exposed to the increased pressure load. Vessels were mounted on a myograph, and their media thickness, lumen diameter, and maximum active wall tension response were measured. In the mesenteric vessels media thickness had increased by 58%, whereas no changes were seen in the renal vessels. Vessels were then fixed, and serial sections were made in the mesenteric vessels. The disector was used to calculate the numerical cell density in each vessel. By combining the myograph measurements and the estimated numerical cell density, the number of cells per segment unit length was calculated (renal hypertensive rats, 6.8 micron-1; sham-operated Wistar-Kyoto rats, 6.3 micron-1; p greater than 0.40) and mean cell volume was determined (renal hypertensive rats, 1541 micron 3; sham-operated Wistar-Kyoto rats, 1256 micron 3; p less than 0.02). No morphometrical changes were found in single sections of the renal arteries. We conclude that the increased media thickness observed in mesenteric resistance vessels of one-kidney, one clip Goldblatt hypertensive rats mainly was caused by smooth muscle cell hypertrophy.
Cardiopulmonary reflex before and after regression of left ventricular hypertrophy in essential hypertension.
Authors: Grassi G , Giannattasio C , Cléroux J , Cuspidi C , Sampieri L , Bolla G B , Mancia G
Published: June 2012

Studies that have examined the cardiopulmonary receptor control of circulation in hypertension have produced conflicting results. In 10 normotensive subjects and in age-matched essential hypertensive subjects without (n = 10) or with left ventricular hypertrophy (n = 12), as well as in seven subjects of the latter group restudied after 1 year of treatment that induced regression of cardiac hypertrophy, we examined the cardiopulmonary reflex by increasing central venous pressure and stimulating cardiopulmonary receptors through passive leg raising and by reducing central venous pressure and deactivating cardiopulmonary receptors through nonhypotensive lower body negative pressure. Reflex responses were measured as changes in forearm vascular resistance (mean blood pressure divided by plethysmographically measured blood flow), plasma norepinephrine concentration, and plasma renin activity. In hypertensive subjects without left ventricular hypertrophy, stimulation and deactivation of cardiopulmonary receptors caused changes in forearm vascular resistance, norepinephrine concentration, and plasma renin activity that were modestly reduced as compared with those in normotensive subjects. However, all these changes were markedly reduced in hypertensive subjects with left ventricular hypertrophy. Following regression of left ventricular hypertrophy, the changes in vascular resistance, plasma norepinephrine, and plasma renin activity induced by cardiopulmonary receptor manipulation all improved markedly. These results demonstrate that cardiopulmonary receptor regulation of peripheral vascular resistance and of neurohumoral variables is impaired in essential hypertension and that the impairment is much more pronounced when this condition is associated with cardiac structural alterations. Therapeutic regression of these alterations, however, leads to a marked improvement of this reflex, with consequent favorable effects on circulatory homeostasis.
Dipyridamole echocardiography in essential hypertensive patients with chest pain.
Authors: Picano E , Lucarini A R , Lattanzi F , Distante A , Di Legge V , Salvetti A , L'Abbate A
Published: June 2012

The exercise-electrocardiography test shows limited feasibility and diagnostic accuracy for the noninvasive detection of coronary artery disease in hypertensive patients. Recently, the dipyridamole-echocardiography test (two-dimensional echocardiographic monitoring with dipyridamole infusion, up to 0.84 mg/kg over 10 minutes) has been proposed as an exercise-independent method for the diagnosis of coronary artery disease. The diagnostic usefulness of the exercise-electrocardiography test and the dipyridamole-echocardiography test was evaluated in 63 consecutive inpatients with history of chest pain, essential hypertension, and no previous myocardial infarction. The criterion of positivity for the exercise-electrocardiography test was a horizontal or downsloping ST segment shift exceeding 0.1 mV and for the dipyridamole-echocardiography test, a transient dyssynergy of contraction. Fifteen patients could not perform a diagnostic exercise-electrocardiography test because of an inability to exercise adequately (two patients), severe hypertension in spite of full antihypertensive therapy (six patients), or excessive blood pressure rise at the first step of the exercise-electrocardiography test (seven patients). Five patients could not perform the dipyridamole-echocardiography test because of a poor acoustic window. The overall feasibility was 76% for the exercise-electrocardiography test and 92% for the dipyridamole-echocardiography test (p less than 0.05). All 43 patients who performed both tests underwent coronary angiography; 30 had significant coronary artery disease (greater than 70% lumen reduction of at least 1 major coronary vessel). Sensitivity was 67% for both the exercise-electrocardiography test and the dipyridamole-echocardiography test (p = NS); specificity was 46% for the exercise-electrocardiography test and 92% for the dipyridamole-echocardiography test (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
Volume (weight) loss and blood pressure response following thiazide diuretics.
Authors: Freis E D , Reda D J , Materson B J
Published: June 2012

Correlations were made between weight change (as an index of volume loss) and blood pressure (BP) reduction before and after hydrochlorothiazide treatment. A total of 343 patients with mild to moderate hypertension (95-114 mm Hg) received hydrochlorothiazide alone. The diuretic was titrated from 50 to 100 to 200 mg daily as needed until the diastolic BP fell below 90 mm Hg (goal BP) or side effects supervened. Of the 305 patients who completed the 10-week titration period, 65% attained goal BP. The effective dose of hydrochlorothiazide in 52% of these responders was 50 mg/day, and this was associated with weight loss averaging 1.58 kg. An additional 29% achieved goal BP with a similar degree of weight loss, but they required double the dose, or 100 mg/day. The remaining 19% of responders required significantly greater weight reductions averaging 3.14 kg to achieve goal BP, which necessitated hydrochlorothiazide, 200 mg/day. More blacks than whites attained goal BP despite similar degrees of weight loss in the two races. Plasma renin activity was initially higher in whites than in blacks and rose significantly more in blacks and whites requiring the greatest volume losses and the highest dose of hydrochlorothiazide to attain goal BP. Nonresponders had less weight loss than responders. Thus, diuretic dose requirements vary in different patients and are related either to different volume losses in response to a given dose or to different degrees of BP reduction in response to the same volume loss.
Influence of race, sex, and blood pressure on erythrocyte sodium transport in humans.
Authors: Smith J B , Wade M B , Fineberg N S , Weinberger M H
Published: June 2012

Sodium transport of erythrocytes from normotensive and essential hypertensive subjects was evaluated by determining ouabain-sensitive and ouabain-insensitive sodium efflux rates, Na+-Li+ countertransport rates, Li+-K+ cotransport rate constants (lithium replacing sodium), intracellular sodium concentrations, and the number of Na+,K+-adenosine triphosphatase (ATPase) sites per erythrocyte. Subjects included men and women, blacks and whites. Hypertensive subjects had significantly higher sodium transport than did normotensive subjects for ouabain-sensitive sodium efflux (p less than 0.025) and Na+-Li+ countertransport (p less than 0.001). Sexual differences were noted for ouabain-sensitive (p less than 0.001) and ouabain-insensitive (p less than 0.001) sodium efflux, for intracellular sodium concentration (p less than 0.025), and for the Li+-K+ cotransport rate constant (p less than 0.005), all with higher values for men than for women. Racial differences were noted for ouabain-insensitive sodium efflux (p less than 0.005), Na+-Li+ countertransport (p less than 0.001), and the Li+-K+ cotransport rate constant (p less than 0.001); values were higher in whites than blacks for all three measurements. The number of [3H]ouabain binding sites was lower for blacks (p less than 0.001) and the intracellular sodium concentration was higher for blacks (p less than 0.001). Among all subjects, significant (p less than 0.001) correlations were found between intracellular sodium concentration and the number of Na+,K+-ATPase sites per erythrocyte (r = -0.78) and between the ouabain-sensitive sodium efflux per site and intracellular sodium concentration (r = 0.85, p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)
Adrenal-dependent change in vascular reactivity in stroke-prone spontaneously hypertensive rats.
Authors: Bruner C A , Webb R C
Published: June 2012

Tail arteries from stroke-prone spontaneously hypertensive rats (SHRSP) exhibit oscillatory contractions in response to norepinephrine. This type of oscillatory behavior does not occur in tail arteries from normotensive Wistar-Kyoto rats (WKY). We have shown that the traits of norepinephrine-induced oscillatory activity and high blood pressure are genetically associated in SHRSP, suggesting that oscillatory activity is a primary vascular abnormality that contributes to hypertension in this strain. In the present experiments, two approaches were used to test the hypothesis that adrenal mineralocorticoids modulate expression of this genetically determined vascular abnormality in SHRSP. First, the effect of adrenalectomy on blood pressure and oscillatory activity was determined in SHRSP that underwent bilateral adrenalectomy 3 weeks before experimentation. Second, the effect of deoxycorticosterone acetate (DOCA)-salt treatment on blood pressure and oscillatory activity was determined in 1) rats with no genetic background for oscillatory activity (WKY) and 2) progeny of SHRSP x WKY (F1 rats). Helically cut tail artery strips from all rats were mounted in isolated tissue baths for isometric force recording. Vessels were exposed to norepinephrine (6 x 10(-10) to 6 x 10(-6) M) for 20 minutes at each concentration. Oscillatory activity was defined as the sum of the phasic contractile amplitudes for all oscillations occurring during the final 10 minutes of norepinephrine incubation. Adrenalectomy markedly decreased blood pressure and oscillatory activity in SHRSP.(ABSTRACT TRUNCATED AT 250 WORDS)
Possible involvement of brain opioid peptides in clonidine-induced hypotension in spontaneously hypertensive rats.
Authors: van Giersbergen P L , Tierney S A , Wiegant V M , de Jong W
Published: June 2012

The effect of intracisternal pretreatment with opiate antagonists or antisera against various opioid peptides on the hypotension and bradycardia induced by cumulative intracisternal administration of clonidine (0.02-2.5 microgram) was studied in conscious Wistar-Kyoto rats and in spontaneously hypertensive rats. No effect of any pretreatment on basal values of blood pressure and heart rate was detected in either of these strains. In spontaneously hypertensive rats intracisternal pretreatment with naltrexone resulted in a dose-dependent inhibition of clonidine-induced hypotension and bradycardia. DL-naloxone also antagonized the hypotension but not influence the hypotensive and bradycardic response to clonidine. In Wistar-Kyoto rats naltrexone and the beta-endorphin antiserum B4 failed to affect the cardiovascular effects of clonidine. B4 and an antiserum against dynorphin(1-13) inhibited clonidine-induced hypotension in spontaneously hypertensive rats, whereas a [Met5]enkephalin antiserum had no effect. Use of antisera specifically recognizing the C-terminus of beta-, alpha-, and gamma-endorphin, respectively, revealed that only the beta-endorphin antiserum inhibited the fall in blood pressure in spontaneously hypertensive rats after cumulative administration of clonidine. None of the antisera used affected clonidine-induced bradycardia. These results indicate that activation of stereospecific opiate receptors in spontaneously hypertensive, but not in Wistar-Kyoto rats, plays a role in the central hypotensive effect of clonidine. beta-Endorphin(1-31) and dynorphin(1-13) might be the endogenous ligands for these receptors.
Atrial natriuretic factor inhibits isoproterenol- and furosemide-stimulated renin release in humans.
Authors: McMurray J J , Struthers A D
Published: June 2012

The effects of atrial natriuretic factor (0.025 microgram/kg/min) on isoproterenol-(0.02 microgram/kg/min) and furosemide-(5 mg i.v. bolus) stimulated renin release were studied in seven salt-replete healthy volunteers. Isoproterenol or furosemide were given against a background infusion of 5% D-glucose (placebo day) or atrial natriuretic factor (experimental day). Atrial natriuretic factor abolished the rise in plasma renin activity caused by isoproterenol (p = 0.003) and significantly (p = 0.048) attenuated the rise in plasma renin activity after a bolus injection of furosemide. These results show that a pharmacological dose of atrial natriuretic factor inhibits stimulated renin release in humans. This attenuation is apparent with two heterogenous stimuli, which suggests a nonspecific effect.
Renin regulation in type II diabetes mellitus: influence of dietary sodium.
Authors: Trujillo A , Eggena P , Barrett J , Tuck M
Published: June 2012

Numerous abnormalities in the renin-angiotensin system have been described in diabetes mellitus. Plasma renin activity (PRA) has been noted to be low, normal, and high in diabetic patients; these variable results may be explained by differences in patient selection and standardization of study conditions. We evaluated PRA and inactive renin responses in Type II normotensive (n = 7) and hypertensive (n = 12) diabetic patients specifically selected for no or minimal evidence (background retinopathy) for microvascular complications. Patients were studied in a metabolic ward after 7 days on a constant low sodium (20 meq/day) and 7 days on a high sodium (250 meq/day) diet. Nondiabetic control subjects (n = 7) were evaluated under similar conditions. On low sodium intake, mean PRA levels were significantly reduced in the hypertensive diabetic group, but were not different between the control and normotensive diabetic groups. Hypertensive diabetic patients on high sodium intake also had greater reductions in PRA responses compared with the other study groups. In general, diabetic subjects on high sodium intake excreted less sodium and had more cumulative sodium retention than control subjects. Levels of inactive renin were not significantly different between the normotensive and hypertensive diabetic patients and were comparable with the levels in control subjects. Inactive renin levels changed in a similar direction and magnitude as PRA in response to sodium intake and posture in the three study groups. Infusion of angiotensin II led to comparable reductions in PRA in both diabetic groups and in the control group, suggesting an intact short feedback loop control.(ABSTRACT TRUNCATED AT 250 WORDS)