bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of sodium salts on pressor reactivity in salt-sensitive men.
Authors: Sharma A M , Schattenfroh S , Thiede H M , Oelkers W , Distler A
Published: June 2012

Blood pressure in patients with essential hypertension is raised by sodium chloride but not by nonchloride sodium salts. Although a high sodium chloride diet is known to augment the pressor response to norepinephrine and angiotensin II, the effect of nonchloride sodium salts on pressor responsiveness has not been studied so far. To examine whether sodium chloride and nonchloride sodium salts evoke different pressor responses to these agonists, we performed graded norepinephrine and angiotensin II infusions in salt-sensitive (n = 7) and salt-resistant (n = 8) normotensive subjects. The subjects were given a low salt diet (20 mmol/day) for 3 weeks, to which a supplement of 200 mmol sodium per day, provided as either sodium chloride or sodium citrate, or a placebo was added for 1 week each. We found that, although sodium chloride raised mean arterial blood pressure in the salt-sensitive subjects (p less than 0.005), sodium citrate did not. However, under both sodium salts pressor response to norepinephrine and angiotensin II was significantly greater than under placebo (p less than 0.02). Furthermore, with both sodium salts, pressor response in the salt-sensitive subjects was greater than in the salt-resistant subjects (p less than 0.01). This study thus demonstrates that, although blood pressure in salt-sensitive individuals is raised by sodium chloride only, both sodium chloride and sodium citrate evoke similar increases in pressor response to norepinephrine and angiotensin II. Since pressor response increased with both sodium salts but resting blood pressure increased only with sodium chloride, enhanced pressor responsiveness alone cannot account for the sodium chloride-induced rise in resting blood pressure.
Increased vascular formation of angiotensin II in one-kidney, one clip hypertension.
Authors: Leite R , Salgado M C
Published: June 2012

To assess the role of the vascular angiotensin II-generating system in one-kidney, one clip hypertension, we determined the angiotensin converting enzyme activity in plasma and vascular tissues and examined the pressor response to angiotensin II, angiotensin I, and tetradecapeptide renin substrate in isolated mesenteric arteries from one-kidney, one clip hypertensive rats 7 and 30 days after clipping the renal artery and in mesenteric arteries from age-matched normotensive rats. Angiotensin converting enzyme activity, determined in aortic and mesenteric tissues, was significantly augmented in the hypertensive (30 days after clipping) group, whereas plasma activity was normal. The vasoconstrictor responses elicited by angiotensin I and tetradecapeptide in arteries from hypertensive rats were found to be significantly potentiated 30 days after clipping, whereas the angiotensin II responses were basically unchanged. Saralasin completely blocked the vasoconstrictor responses, whereas captopril blocked only the responses to angiotensin I without affecting the responses elicited by angiotensin II and tetradecapeptide. Enalapril, an angiotensin converting enzyme inhibitor given intravenously to unanesthetized rats, significantly lowered the blood pressure of hypertensive rats. The pressor responses elicited by angiotensin II, angiotensin I, and tetradecapeptide were completely inhibited by saralasin, whereas enalapril blocked only the responses of angiotensin I but not those elicited by angiotensin II and tetradecapeptide. These results indicate that local formation of angiotensin II is increased in arteries of one-kidney, one clip hypertensive rats. The data obtained with tetradecapeptide renin substrate suggest an important role for nonrenin proteases in vascular angiotensin II formation.
Defective dopamine generation from dihydroxyphenylalanine in stable essential hypertensive patients.
Authors: Kuchel O , Shigetomi S
Published: June 2012

We studied the metabolic pathways of dihydroxyphenylalanine (DOPA) and dopamine as well as the cardiovascular and renal responses to a single administration of DOPA (500 mg orally) in stable essential hypertension. We found that after DOPA, stable hypertensive patients compared with controls showed more blood pressure decrease without reflex tachycardia, had lower creatinine clearance but a higher fractional excretion of sodium, and had lower plasma renin activity at the height of DOPA action. Hypertensive patients also showed increased plasma DOPA, the ratio of plasma DOPA to dopamine, and the sum of plasma DOPA and 3-O-methyl-DOPA, as well as increased urinary 3-O-methyl-DOPA and the plasma and urine dopamine metabolites 3,4-dihydroxyphenylacetic acid and homovanillic acid. Finally, despite an augmented post-DOPA glomerular load of DOPA, the predominant source of urinary dopamine, the excretion rates of dopamine and its metabolites remained comparable in hypertensive patients to those in control subjects. These data suggest that, in stable hypertensive patients, exogenous DOPA is to a lesser degree decarboxylated to dopamine, which is more rapidly metabolized intraneuronally. Contrasting with this finding are the hyperdopaminergic features, such as hypernatriuresis with renin suppression and excessive blood pressure decline in the absence of reflex tachycardia. They may be due to an upregulation of renal, vascular, and brain dopaminergic receptors secondary to a preexisting dopaminergic deficiency in stable essential hypertension.
Polymerase chain reaction analysis of renin in rat aortic smooth muscle.
Authors: Holycross B J , Saye J , Harrison J K , Peach M J
Published: June 2012

Controversy exists whether vascular smooth muscle cells in vivo synthesize renin, thereby providing a critical component of the hypothesized vascular renin-angiotensin system. To examine this question, we enzymatically isolated and pooled the medial layer of thoracic aortas from Sprague-Dawley rats that were either untreated or enalapril treated for 3 days, isolated messenger RNA (mRNA), and performed Northern blot analysis with rat complementary DNA (cDNA) probes for renin, cathepsin D, and cathepsin E. Renin mRNA was detected in kidney but was not detected in aortic smooth muscle from the untreated or enalapril-treated groups. Cathepsin E mRNA was detected in enalapril-treated aorta and kidney, and cathepsin D mRNA was detected in all tissues examined. cDNA was synthesized and subjected to polymerase chain reaction analysis by using primers corresponding in sequence to regions conserved throughout the aspartic proteinases. Cathepsins D and E were amplified from kidney and aortic cDNA. Renin was less consistently amplified from the aortic cDNA and was much less abundant than cathepsin E or cathepsin D. These results suggest that 1) renin mRNA is present in aortic smooth muscle cells in vivo in quantities detectable only after multiple rounds of polymerase chain reaction amplification, 2) renin mRNA is not upregulated in aortic smooth muscle after converting enzyme inhibition, and 3) cathepsins D and E are the predominant aspartic proteinases in aortic smooth muscle.
Signal transduction pathways in constriction of the basilar artery in vivo.
Authors: Murray M A , Faraci F M , Heistad D D
Published: June 2012

We examined effects of a putative myosin light chain kinase inhibitor in the cerebral circulation in vivo. In anesthetized rats, diameter of basilar arteries was measured through a cranial window (control, 232 +/- 10 microns, mean +/- SEM). Vessel diameter was measured during topical application of agonists and antagonists. ML-7, which has been reported to compete with adenosine triphosphate for binding to the catalytic site on myosin light chain kinase, attenuated vasoconstriction in response to prostaglandin F2 alpha (10(-6) M; -22 +/- 1% before versus -14 +/- 1% and -3 +/- 2% during ML-7, 10(-7) and 10(-6) M, respectively; p less than 0.05). ML-7 (10(-6) M) did not affect baseline diameter. Responses to serotonin (10(-8) M) and phorbol 12,13-dibutyrate (10(-8) M) were not attenuated by ML-7. Thus, constriction of the basilar artery induced by prostaglandin F2 alpha in vivo is attenuated by an inhibitor of myosin light chain kinase.
Nitric oxide modulates vascular tone in preglomerular arterioles.
Authors: Imig J D , Roman R J
Published: June 2012

Blockade of nitric oxide reduces renal blood flow, but the site or sites at which nitric oxide alters renal vascular resistance are unknown. The effects of N omega-nitro-L-arginine (100 microM), an inhibitor of nitric oxide synthesis, on the pressure-diameter relation of renal arterioles was studied using a rat juxtamedullary microvascular preparation perfused in vitro with a physiological salt solution containing 5% albumin. The basal diameters of the main arcuate and interlobular arteries and the proximal and distal afferent arterioles averaged 438 +/- 26, 64 +/- 4, 30 +/- 1, and 20 +/- 1 microns, respectively, at a perfusion pressure of 80 mm Hg. The diameters of the arcuate and interlobular arteries increased by 14 +/- 2% and 7 +/- 2%, whereas the proximal and distal afferent arterioles decreased by 3 +/- 1% and 7 +/- 2% when perfusion pressure was elevated to 160 mm Hg. Nitro-arginine had no effect on the basal diameters of arcuate and interlobular arteries. Nitro-arginine reduced the diameters of afferent arterioles by 7 +/- 2% at all perfusion pressures studied. Nitro-arginine increased active vascular tone in the interlobular artery and afferent arterioles and enhanced autoregulation of glomerular capillary pressure. L-Arginine (1 mM), the precursor to nitric oxide production, reversed the effects of nitro-arginine. These findings suggest that nitric oxide modulates vascular tone of the interlobular artery and afferent arterioles of deep nephrons and influences the ability of the preglomerular vasculature to autoregulate glomerular capillary pressure.
Norepinephrine in urine and plasma following provocative maneuvers in normal and hypertensive subjects.
Authors: Henry D P , Luft F C , Weinberger M H , Fineberg N S , Grim C E
Published: June 2012

Urinary norepinephrine (UNE) excretion rate and venous plasma norepinephrine (PNE) concentrations were studied in 266 normotensive and 107 essential hypertensive men and women under conditions of volume expansion with 2 liters of intravenous normal saline over 4 hours, and volume contraction with a 10 mEq sodium diet and 120 mg oral furosemide. The UNE excretion rate was correlated with age in normal women only. In men, and in hypertensives of both sexes, the relationship appeared to be biphasic. The PNE concentration was not correlated with age in the hypertensive subjects. Insufficient numbers of older subjects were available to exclude absolutely such a relationship among normals. The UNE and PNE were influenced by volume expansion and contraction in both normals and hypertensives; however, normals exhibited a correlation between UNE and blood pressure as well as consistent correlations between UNE and PNE, neither of which were observed in the hypertensives. Hypertensive women generally had greater UNE and PNE values than normal women or hypertensive men. Hypertensive women may have altered sympathetic activity.
Enhanced parathyroid function in essential hypertension: a homeostatic response to a urinary calcium leak.
Authors: McCarron D A , Pingree P A , Rubin R J , Gaucher S M , Molitch M , Krutzik S
Published: June 2012

Disorders of calcium metabolism are not generally considered important either clinically or pathophysiologically in essential hypertension. Recent reports, though, suggest that increased parathyroid gland function may be one of the more common endocrine disturbances associated with hypertension. We measured serum parathyroid hormone (PTH) concentrations as well as routine blood and urine chemistries in 34 hypertensives. Their mean PTH, 79.1 +/- 3.1 muliter Eq/muliter, was significantly higher (p less than 0.025) than the mean PTH, 66.9 +/- 3.3, of an age- and sex-matched normotensive control population. The mean serum calcium, 9.5 +/- 0.1 mg%, was identical in the two populations. Compared to a second age- and sex-matched normotensive population, the hypertensives demonstrated a significant (p less than 0.005) relative hypercalciuria. For any level of urinary sodium, hypertensives excreted more calcium. These preliminary data suggest that parathyroid gland function may be enhanced in essential hypertension. This increased gland activity appears, in part, to be an appropriate, physiologic response to a previously unrecognized relative hypercalciuria, or renal calcium leak, associated with essential hypertension. We conclude that the increased prevalence of hypertension in subjects with hyperparathyroidism probably represents the final event in a continuum that begins with obligatory urinary calcium losses in hypertensives, but whose pathological presentation is hyperparathyroidism. The results of this pilot study indicate a need for derivative experiments directed at defining the importance of our preliminary findings in the pathogenesis of human and experimental hypertension.
Hypertension following coronary artery bypass surgery. Role of preoperative propranolol therapy.
Authors: Whelton P K , Flaherty J T , MacAllister N P , Watkins L , Potter A , Johnson D , Russell R P , Walker W G
Published: June 2012

Over a 9-month period, the incidence and characteristics of hypertension following coronary artery bypass surgery were studied in a group of 52 patients. Hypertension occurred in 61% of the patients and was characterized by an increase in arterial blood pressure of 35 +/- 2 mm Hg mean +/- SEM during the early postoperative period. Preoperative blood pressures and hemodynamic variables were similar in those who developed hypertension of those who remained normotensive. Ninety-four percent of those who developed hypertension as compared to only 40% of those who remained normotensive received propranolol during the 24 hours preceding surgery (x2 = 15.4; p less than 0.001). Maximal blood pressures during the first 5 hours following the termination of cardiopulmonary bypass were significantly positively correlated with preoperative propranolol dosage (p less than 0.01). Hypertension was not associated with significant changes in plasma renin activity or angiotensin II levels, but concomitant plasma catecholamine concentrations were elevated significantly (p less than 0.005). However, a similar rise in plasma catecholamine concentrations was found in those who remained normotensive. Hypertension was associated with an increase in systemic vascular resistance (p less than 0.001) and left ventricular stroke work index (p less than 0.05), and a fall in stroke volume (p less than 0.005) and cardiac index (p less than 0.001). These studies suggest that hypertension following coronary artery bypass surgery is common, results from an increase in systemic vascular resistance, is not renin-angiotensin mediated, and may, in part, be related to preoperative propranolol administration.
Hemodynamic response to vascular expansion following immunosympathectomy in spontaneously hypertensive rats.
Authors: Cutilletta A F , Oparil S
Published: June 2012

Spontaneously hypertensive male rats (SHR) or normotensive Kyoto-Wistar (WKY) male rats underwent either sham or nerve growth factor antiserum (NGFAS) treatment during the first week of life. The NGFAS treatment prevented the development of hypertension in SHR but did not prevent the development of left ventricular groups in vivo under general anesthesia. After the recording of resting parameters, homologous whole blood was transfused until the rise in cardiac output reached a plateau. At rest, LV systolic pressure of the NGFAS-treated SHR was significantly lower than that of the sham-treated SHR and not statistically different from that of the WKY rat. The LV end diastolic pressures did not differ among the four groups. Both SHR groups had significantly lower cardiac, stroke, and contractility indices than di the WKY groups. Following vascular expansion, LV filling pressure, stroke index, and stroke work index rose in all groups. The response in the SHR was greater than that in WKY groups. Interestingly, the systolic pressure of the NGFAS-treated SHR rose to the same level as in the sham-treated SHR. Heart rate and calculated systemic vascular resistance fell following transfusion. The SHR appears to exhibit an altered response to increased filling pressure and increased afterload. Our findings are consistent with the concept of an alteration in the compliance of the LV in the SHR.
Spontaneous remission of hypertension in awake rats chronically exposed to shaker stress.
Authors: Buñag R D , Takeda K , Riley E
Published: June 2012

Hypertension was induced experimentally by subjecting rats to vigorous shaking, 4 hours (at random) daily for 14 weeks. Systolic pressures measured with the tail-cuff method began to rise after the first week and were significantly elevated on Weeks 3, 4, 6, 7, and 8, but reverted to normotensive levels thereafter despite continued shaking. A similar hypertension was then induced in another group of rats and when spontaneous remission occurred, pressor responsiveness was tested on the eleventh week by recording aortic pressures from indwelling catheters. Pressor responses to further shaking or electrical stimulation of the anterior hypothalamus were smaller in shaker-stressed than in control rats, while those to injected norepinephrine were almost the same in both groups. Spike potentials recorded from postganglionic sympathetic (splanchnic) nerves showed higher baselines but smaller increases in neural firing during hypothalamic stimulation in shaker-stressed than in control rats. These results suggest that while shaker stress alone can induce hypertension, the resulting blood pressure elevation is not sustained, perhaps because adaptation within the central nervous system concurrently reduces pressor responsiveness.
Factors determining direct arterial pressure and its variability in hypertensive man.
Authors: Watson R D , Stallard T J , Flinn R M , Littler W A
Published: June 2012

Intra-arterial pressure was recorded continuously in 26 patients with uncomplicated essential hypertension under standardized conditions. Recordings were analyzed beat by beat to obtain mean pressures and variability, expressed as the standard deviation of the frequency histogram. The major factors influencing variability were the level of pressure and the intensity of physical activity; systolic variability increased with progressive impairment of sino-aortic baroreflexes. Diastolic pressure increased with the level of sympathetic activity as reflected by plasma norepinephrine levels. After allowance for the decrease of plasma renin activity (PRA) with age, direct relationships were observed between PRA (log values) and the level of pressure and systolic variability; plasma angiotensin II values did not correlate. Systolic variability increased with the systolic response to cold but was unrelated to the response to dynamic or isometric exercise. Variability also tended to increase with obesity and was unrelated to age, sex, or race.
Enkephalin effects on blood pressure, heart rate, and baroreceptor reflex.
Authors: Schaz K , Stock G , Simon W , Schlör K H , Unger T , Rockhold R , Ganten D
Published: June 2012

The cardiovascular effects of opioid peptides have been studied. Leucine-enkephalin (Leu-ENK) produced blood pressure (BP) increases following administration into the lateral brain ventricles (i.v.t.), into the cisterna magna (i.c.i.), and following intravenous (i.v.) administration. Heart rate (HR) increases were observed following all routes of administration (threshold for BP and HR effects at 0.3 nmole, maximum at 360 nmoles). The cardiovascular effects were independent of generalized seizures, which may occur at higher doses of enkephalins (ENK). D-alanine-enkephalin (D-Ala-ENK) attenuated the vagal component of the baroreceptor reflex in cats. This was indicated by the findings that HR did not decrease following D-Ala-ENK-induced BP increases and that the compensatory decreases in HR following i.v. pressor doses of angiotensin II (ANG II) were markedly attenuated in cats treated with i.v.t. D-Ala-ENK. Naloxone inhibited the BP and HR effects following i.c.i. and i.v., but not following i.v.t., administration of Leu-ENK. The i.v.t. Leu-ENK effect were inhibited by beta-adrenergic receptor blockade. Bratteboro rats homozygous for hereditary diabetes insipidus with total absence of antidiuretic hormone (ADH) synthesis responded with BP decreases following i.v.t. Leu-ENK, while BP increases were observed in control Long-Evans rats. Blood pressure increases to i.v.t. Leu-ENK were markedly greater in spontaneously hypertensive rats of the stroke-prone strain (SHR-sp) than in normotensive control rats; SHR-sp exhibit a humoral pattern of increased ADH, ACTH, and catecholamines, presumably due to central peptidergic stimulation. The known effects of opioid peptides on these hormones and the observed cardiovascular responses suggest a possible participation of this peptide system in the maintenance of high BP in the SHR-sp.
Effect of salt on the vascular lesions of spontaneously hypertensive rats.
Authors: Limas C , Westrum B , Limas C J , Cohn J N
Published: June 2012

High salt intake accelerates hypertension in humans and increases cardiovascular morbidity and mortality. The temporal relation between blood pressure (BP) elevation and appearance of vascular lesions during salt-loading was studied in the spontaneously hypertensive rat (SHR). Starting at 5 weeks of age, SHRs and normotensive Wistar-Kyoto rats (WKYs) were given 1% NaCl in their drinking water SHRs and WKYs on tap water served as controls. Animals from each group were sacrificed at 10 and 20 weeks of age, and the aorta and intrarenal vessels were studied by light and electron microscopy. Neither BP nor vascular morphology of WKYs were affected by 1% NaCl. In SHRs, the course of BP was not affected by the addition of salt for at least 11 weeks, but vascular changes were significantly aggravated within 5 weeks. Thus, aortic intimal lesions progressed more rapidly so that, by 20 weeks of age, 50% of the animals had 3+lesions while, in control SHRs, they did not exceed the 2+grade. Salt-loading resulted in significant thickening of the aortic media between the 10th and 20th week of age while control SHRs showed no increment within the same time interval. Also, small intrarenal arterial vessels of salt-treated SHRs had significantly narrower lumina and greater wall thickness at both 10 and 20 weeks of age. In addition, they showed intimal proliferations and necrotizing lesions which were absent from control SHRs at these ages. These results show that, in this experimental model, the aggravation of vascular changes is not merely a sequela of further elevation of BP. Since the adverse effect of salt on the vessels was not seen in WKYs, it is likely that this effect is related to genetic factors or to higher susceptibility of hypertensive vessels.
Converting enzyme inhibition and the kidney.
Authors: Meggs L G , Hollenberg N K
Published: June 2012

We review information on the renal response to converting enzyme inhibition, and attempt to evaluate the evidence that a reduction in angiotensin II formation is responsible for the renal response. There is little response to converting enzyme inhibitors in animals or man when the renin-angiotensin system is suppressed by a literal sodium intake. With restriction of sodium intake, an increase in renal blood flow occurs; because a quantitatively similar response occurs to the angiotensin II analogs it is likely that the response reflects reversal of the local action of angiotensin II. In other settings it is not yet clear whether the renal response to converting enzyme inhibitor reflects only a reduction in angiotensin II formation or an additional action such as potentiation of the local actions of bradykinin or enhanced prostaglandin formation. Because these agents induce a potentiated increase in renal blood flow in the patient with essential hypertension, and with it an increase in glomerular filtration rate and sodium excretion in some patients, despite a fall in arterial pressure these questions have considerable importance.
Studies on the activation and molecular weight of inactive renin in human plasma.
Authors: Morimoto K , Matsunaga M , Hara A , Kawai C
Published: June 2012

The mechanism of activation of inactive renin was studied in normal human plasma. The molecular weight of active renin and those of inactive renin before and after activation were analyzed by sephadex gel filtration. Active renin of human plasma had a molecular weight of 48,000 +/- 1000. Trypsin treatment and cold treatment activated inactive renin of a molecular weight of 54,000 +/- 1000. The inactive renin apparently did not change its molecular weight after activation. "Cryoactivation" of inactive renin was possible only when whole plasma was used. When the whole plasma was fractionated by gel filtration, cryoactivation was not observed in any of the fractions. Cryoactivation requires certain plasma factor(s) contained in some fractions. Plasma kallikrein is likely to be a major factor required for the cryoactivation of inactive renin, whereas some other factors may also participate in this mechanism.
Effects of prazosin on autonomic control of circulation in essential hypertension.
Authors: Mancia G , Ferrari A , Gregorini L , Ferrari M C , Bianchini C , Terzoli L , Leonetti G , Zanchettie A
Published: June 2012

Prazosin, an antihypertensive agent that reduces blood pressure (BP) mainly through a blockade of alpha-adrenergic receptors, may, in theory, affect sympathetic control of circulation to an extent that impairs circulatory hemeostasis. This possibility was studied in subjects with essential hypertension by examining the cardiovascular effects of several stimuli that induce a powerful and diversified activation of the sympathetic noradrenergic activity (dynamic and isometric exercise, cold exposure) and of stimuli that exert a powerful inhibitory influence upon the sympathetic nervous system (carotid baroreceptor reflex). Before and after 15 days of continuous administration of prazosin (2-5 mg), 3 times a day, measurements were made of BP (intraarterial catheter), heart rate, cardiac output (thermodilution), and peripheral resistance. Prazosin reduced mean arterial pressure (10%) and peripheral resistance (9%) at rest, and it did not affect heart rate and cardiac output. Neurally mediated changes in arterial pressure, cardiac output, and peripheral resistance during dynamic or isometric exercise and cold exposure were unaffected by the drug; also unaffected were the cardiovascular responses to increase and decrease in carotid baroreceptor activity obtained by varying carotid transmural pressure through a variable neck pressure chamber device. Thus, the hypotensive and vasodilating effect of prazosin in essential hypertension is not accompanied by an impaired response to neural excitation influences upon the cardiovascular system. Also, the inhibitory influences originating from the carotid baroreflex are unchanged. These data indicate that circulatory homeostasis is largely preserved during administration of prazosin at clinically effective doses.
Inactive renin of high molecular weight (big renin) in normal human plasma. Activation by pepsin, trypsin, or dialysis to pH 3.3 and 7.5.
Authors: Hsueh W A , Luetscher J A , Carlson E J , Grislis G
Published: June 2012

Normal plasma contains inactive renin, which becomes active when plasma is dialyzed to pH 3.3 and to pH 7.5, or treated with pepsin or trypsin. Under optimal conditions, each of these procedures activated the same quantity of renin, which was not further increased by repeating or combining two procedures, thus suggesting that the same pool of inactive renin was activated by each procedure. When plasma was fractionated by gel filtration, dialysis activated very little renin in eluates. Trypsin activated renin, but under some conditions also destroyed renin. Pepsin fully activated the inactive renin in eluates without evidence of destruction of renin. The pepsin-activated renin of normal plasma eluted from Sephadex G-100 in a peak of apparent molecular weight (MW) 58,000 and from Sephacryl S-200 with apparent MW 53,000, like big renin in plasma of patients with diabetic nephropathy. Inactive renin was usually increased in amount in plasma of sodium-depleted normal men, but the elution volume did not change with sodium intake. When renin was fully activated in plasma incubated with pepsin or trypsin, the apparent MW of the main peak of big renin did not change appreciably. Inactive renin in plasma was usually increased after sodium depletion, but the elution volume did not change. Active renin of normal plasma had an apparent MW near 41,000 on both gels. Thus, we conclude that big renin is present in normal plasma in amounts at least equal to and usually greater than active renin (the ratio depending on sodium intake) and that pepsin activation readily demonstrates big renin in eluates from gel filtration.
Pseudohypertension and the measurement of blood pressure.
Authors: Bos W J , van Goudoever J , Wesseling K H , Rongen G A , Hoedemaker G , Lenders J W , van Montfrans G A
Published: June 2012

Riva-Rocci Korotkoff (RRK) blood pressure measurements may overestimate the intra-arterial pressure (IAP) in individual patients. To study pseudohypertension, defined as an overestimation larger than 10 mm Hg, we compared RRK and IAP measurements in 76 patients. These patients were considered to be at risk for pseudohypertension because of high age, hypertension, or vascular disease. RRK measurements underestimated simultaneously measured systolic IAP values by 6.0 +/- 6.5 (mean +/- SD) mm Hg, whereas simultaneous diastolic RRK readings overestimated the IAP by 1.9 +/- 5.6 mm Hg. Diastolic overestimation increased slightly with age. Vascular rigidity, as measured by counterpressure plethysmography, did not correlate with these errors. Systolic and diastolic pseudohypertension was observed in two and five patients, respectively. Pseudohypertension was only present in the group in which IAP was measured in the aorta. However, the number of patients with systolic and diastolic pseudohypertension could be increased to three and seven by using the average intra-arterial systolic and diastolic pressure during an RRK measurement or to six and 11 by using the IAP during a control period just before an RRK measurement rather than the IAP at the moment of appearance or disappearance of the Korotkoff sounds. The widely diverging prevalence of pseudohypertension described in the literature might be explained because of such different comparison techniques.
Regulation of contraction and relaxation in arterial smooth muscle.
Authors: Rembold C M
Published: June 2012

Intracellular calcium concentration ([Ca2+]i)-dependent activation of myosin light chain kinase and its phosphorylation of the 20-kd light chain of myosin is generally considered the primary mechanism responsible for regulation of contractile force in arterial smooth muscle. However, recent data suggest that the relation between [Ca2+]i and myosin light chain phosphorylation is variable and depends on the form of stimulation. The dependence of myosin phosphorylation on [Ca2+]i has been termed the "[Ca2+]i sensitivity of phosphorylation." The [Ca2+]i sensitivity of phosphorylation is "high" when relatively small increases in [Ca2+]i induce a large increase in myosin phosphorylation. Conversely, the [Ca2+]i sensitivity of phosphorylation is "low" when relatively large increases in [Ca2+]i are required to induce a small increase in myosin phosphorylation. There are two proposed mechanisms for changes in the [Ca2+]i sensitivity of phosphorylation: Ca(2+)-dependent decreases in the [Ca2+]i sensitivity of phosphorylation induced by phosphorylation of myosin light chain kinase by Ca(2+)-calmodulin protein kinase II and agonist-dependent increases in the [Ca2+]i sensitivity of phosphorylation by inhibition of a myosin light chain phosphatase. I will review the proposed mechanisms responsible for the regulation of [Ca2+]i and the [Ca2+]i sensitivity of phosphorylation in arterial smooth muscle.
12-Lipoxygenase products modulate calcium signals in vascular smooth muscle cells.
Authors: Saito F , Hori M T , Ideguchi Y , Berger M , Golub M , Stern N , Tuck M L
Published: June 2012

Previous studies have shown that inhibition of the lipoxygenase pathway of arachidonic acid metabolism can prevent the development of elevated blood pressure in renin-dependent models of hypertension. Agents that inhibit the lipoxygenase pathway such as phenidone and the flavonoid baicalein can selectively attenuate contractile responses to angiotensin II in vivo as well as in isolated vascular tissue. In the present study, the effects of lipoxygenase inhibitors on pressor-induced changes in cytosolic calcium were examined in cultured rat vascular smooth muscle cells using the fluorescent dye fura-2. Two structurally unrelated lipoxygenase inhibitors, baicalein and 5,8,11-eicosatriynoic acid, attenuated angiotensin II-stimulated increases in cytosolic calcium in both normal and calcium-poor buffer. The addition of 5-, 12-, or 15(S)-hydroxyeicosatetraenoic acid alone to the cells had no acute effect on intracellular calcium concentration. However, the addition of 12(S)-hydroxyeicosatetraenoic acid but not 5- or 15(S)-hydroxyeicosatetraenoic acid restored the initial calcium response to angiotensin II in vascular smooth muscle cells pretreated with both inhibitors; 5,8,11-eicosatriynoic acid also reduced [Arg8]-vasopressin and endothelin-stimulated increases in intracellular calcium. The attenuation of vasopressor-induced calcium transients by agents that inhibit lipoxygenase may explain their observed hypotensive effects in vivo. Moreover, lipoxygenase products, in particular 12(S)-hydroxyeicosatetraenoic acid, may act as mediators for the intracellular actions of angiotensin II and possibly other pressor hormones in vascular tissue by regulation of intracellular calcium metabolism.
Increase of angiotensin converting enzyme gene expression in the hypertensive aorta.
Authors: Shiota N , Miyazaki M , Okunishi H
Published: June 2012

To investigate the possible role of vascular angiotensin converting enzyme (ACE) in the development and maintenance of hypertension, we examined aortic ACE messenger RNA (mRNA) levels in two-kidney, one clip (2K1C) hypertensive rats. The blood pressure was increased remarkably at 4 weeks (early stage) after clipping and remained elevated at 12 weeks (chronic stage). The aorta ACE mRNA levels were significantly elevated in both early and chronic stages concurrently with the increases in aortic ACE activity and blood pressure. The plasma renin activity rose markedly at 4 weeks, but returned to the normal level at 12 weeks. Neither ACE activity in the lung and plasma, nor ACE mRNA level in the lung was altered at either stage. The aorta and liver angiotensinogen mRNA levels and renal renin mRNA level were increased at 4 weeks but decreased at 12 weeks. These results indicate that the acceleration of all components in the renin-angiotensin system may contribute to the development of 2K1C hypertension in the early stage. In the chronic stage, the increased vascular ACE induced by the elevated ACE mRNA levels in the aorta may play the primary role in the acceleration of local angiotensin II formation and thus may sustain the hypertension.
Ethnicity, pressor reactivity, and children's blood pressure. Five years of observations.
Authors: Murphy J K , Alpert B S , Walker S S
Published: June 2012

During the 5 years of this investigation, resting blood pressure and pressor reactivity were measured in 292 white children and 46 black children in 1987, 1988, 1989, and 1991. In 1987, all children were in the third grade; in 1991, the children were in the seventh grade. Reactivity was assessed with a standardized psychological stressor, a television video game. Children displayed significant stability of absolute blood pressure and heart rate reactivity between grades 3 and 7. At all examinations, black children demonstrated blood pressure reactivity that was significantly greater in magnitude (both absolute level and change from resting measurements) than that of white children. Black children exhibited significantly greater heart rate reactivity only when defined as change from the resting measurements; absolute levels of heart rate reactivity were comparable for blacks and whites. For black children, blood pressure reactivity in 1987 was the strongest predictor of resting blood pressure (both systolic and diastolic) in 1991. Among white children, resting blood pressure was the strongest predictor of future resting blood pressure. Further research is needed to determine if ethnic differences in children's pressor reactivity are associated with ethnic differences in the prevalence of hypertension.
Brain atrophy in hypertension. A volumetric magnetic resonance imaging study.
Authors: Salerno J A , Murphy D G , Horwitz B , DeCarli C , Haxby J V , Rapoport S I , Schapiro M B
Published: June 2012

To determine whether hypertension, the predominant risk factor for stroke and vascular dementia, is associated with brain atrophy, magnetic resonance imaging (MRI) scans were performed to quantify brain volumes and cerebrospinal fluid spaces. Eighteen otherwise healthy, cognitively normal older hypertensive men (mean +/- SD age, 69 +/- 8 years, duration of hypertension 10-35 years) and 17 age-matched healthy, normotensive male control subjects were studied in a cross-sectional design. Axial proton-density image slices were analyzed using region-of-interest and segmentation analyses. The hypertensive subjects had significantly larger mean volumes of the right and left lateral ventricles (p less than 0.05, both absolute volume and volume normalized to intracranial volume) and a significantly smaller normalized mean left hemisphere brain volume (p less than 0.05) with a trend toward significance for a smaller normalized mean right hemisphere volume (p less than 0.09). Four hypertensive subjects and one healthy control subject were found to have severe periventricular hyperintensities on T2-weighted MRI images. When data for these subjects were removed from the analyses, the normalized lateral ventricle volumes remained significantly larger in the hypertensive group. Lateral ventricle enlargement was not related to age or use of diuretics in the hypertensive group nor to duration of hypertension between 10 and 24 years. Our findings suggest that long-standing hypertension results in structural changes in the brain. Longitudinal studies will determine whether MRI-associated changes are progressive and if such changes identify hypertensive subjects at increased risk for clinically apparent brain dysfunction.
Modulation of norepinephrine release by galanin in rat medulla oblongata.
Authors: Tsuda K , Tsuda S , Nishio I , Masuyama Y , Goldstein M
Published: June 2012

Galanin, a 29-amino acid peptide, is widely distributed in both the central and peripheral nervous systems and is colocalized with catecholamines, although its physiological significance remains to be elucidated. In the present study we investigated the regulatory mechanisms of galanin on norepinephrine release in rat medulla oblongata. In slices of medulla oblongata of Sprague-Dawley rats, galanin inhibited the stimulation-evoked [3H]norepinephrine release in a concentration-dependent manner (fractional release ratio during electrical stimulation: control 0.937 +/- 0.043, mean +/- SEM, n = 6; galanin 1 x 10(-7) M 0.501 +/- 0.037, n = 6, p less than 0.05; and galanin 1 x 10(-6) M 0.299 +/- 0.018 n = 6, p less than 0.05). Galanin potentiated inhibition of [3H]norepinephrine release by the alpha 2-agonists (UK 14,304 and clonidine). The blockade of alpha 2-adrenergic receptors by RX 781094 diminished the inhibition of norepinephrine release by galanin. Pretreatment of pertussis toxin, which interferes with the coupling of inhibitory guanosine triphosphate-binding proteins to adenylate cyclase, significantly attenuated the suppressive effects of galanin on norepinephrine release. In slices of medulla oblongata obtained from spontaneously hypertensive rats (SHR), the inhibitory effect of galanin on norepinephrine release was significantly less than in those from age-matched Wistar-Kyoto rats. These results show that galanin might inhibit the stimulation-evoked norepinephrine release in rat medulla oblongata, at least partially mediated by alpha 2-adrenergic receptors and the pertussis toxin-sensitive guanosine triphosphate-binding proteins. Moreover, less suppression of norepinephrine release by galanin in SHR suggests that galanin might be involved in the regulation of central sympathetic nervous activity in hypertension.
Effect of early onset angiotensin converting enzyme inhibition on myocardial capillaries.
Authors: Unger T , Mattfeldt T , Lamberty V , Bock P , Mall G , Linz W , Schölkens B A , Gohlke P
Published: June 2012

We investigated the preventive effects of long-term treatment with the angiotensin converting enzyme inhibitor ramipril on myocardial left ventricular hypertrophy and capillary length density in spontaneously hypertensive rats. Rats were treated in utero and subsequently up to 20 weeks of age with a high dose (1 mg/kg per day) or with a low dose (0.01 mg/kg per day) of ramipril. Animals given a high dose of ramipril remained normotensive, whereas those given a low dose developed hypertension in parallel to vehicle-treated controls. At the end of the treatment period, converting enzyme activity in heart tissue was inhibited dose-dependently in the treated groups. Both groups revealed an increase in myocardial capillary length density together with increased myocardial glycogen and reduced citric acid concentrations. Left ventricular mass was reduced only in high dose- but not in low dose-treated animals. Our results demonstrate that early onset treatment with a converting enzyme inhibitor can induce myocardial capillary proliferation, even at doses too low to antagonize the development of hypertension or left ventricular hypertrophy. We hypothesize that potentiation of kinins is responsible for this effect, probably by augmenting myocardial blood flow, which is a well-known trigger mechanism of angiogenesis in the heart.
Collagen deposition and the reversal of coronary reserve in cardiac hypertrophy.
Authors: Isoyama S , Ito N , Satoh K , Takishima T
Published: June 2012

The aim of this study was to clarify how collagen deposition or medial hypertrophy of the vascular wall affects the coronary dilator reserve in pressure-overloaded hearts and whether inhibition of collagen deposition reverses the abnormalities after relief of pressure overload. We used ascending aortic banding and debanding methods and superimposed beta-aminopropionitrile in some of the banded rats (50 mg/kg i.p., twice a day). Ten weeks of banding increased in vivo peak systolic left ventricular pressure and produced medial hypertrophy, an increase in collagen deposition in the myocardial and perivascular tissues, and myocardial hypertrophy in the banded group without beta-aminopropionitrile treatment. Superimposition of beta-aminopropionitrile treatment on banding inhibited the increase in collagen deposition. In the groups debanded after the 10-week banding period, both with and without beta-amino-propionitrile treatment, medial and myocardial hypertrophy regressed 4 weeks after debanding. We estimated coronary dilator reserve in Langendorff preparations perfused with modified Tyrode's solution containing oxygenated bovine red blood cells and serum albumin. The ratio of reactive peak flow after brief ischemia-to-resting flow decreased in both of the banded groups. After debanding, the ratio remained lower in the banded group without beta-aminopropionitrile treatment than in the control group. However, debanding in the group with beta-aminopropionitrile treatment increased the ratio to a level similar to that of the control group. Thus, in pressure-overloaded cardiac hypertrophy with coronary hypertension, coronary reserve seems to be determined by medial hypertrophy independently of collagen deposition, but collagen deposition plays an important role in the reversal of vasodilator reserve after relief of the overload.
Effects of alcohol and caloric restrictions on blood pressure and serum lipids in overweight men.
Authors: Puddey I B , Parker M , Beilin L J , Vandongen R , Masarei J R
Published: June 2012

We have examined the independent and combined effects on blood pressure and blood lipids of alcohol restriction and weight loss in overweight male drinkers with a view to assessing overall effects on cardiovascular risk of two widely promoted nonpharmacological approaches for hypertension. Eighty-six men with a mean age of 44.3 years, a mean regular alcohol intake of 440 ml/wk (five or six standard drinks per day), a mean blood pressure of 137.4 mm Hg systolic and 84.8 mm Hg diastolic, and a mean body mass of 92.5 kg entered a controlled two-way factorial study. The subjects were randomly assigned to four groups for an 18-week intervention in which members of two groups drank only low-alcohol beer, thereby reducing their alcohol intake by 374 ml/wk, while those of the other two groups continued their normal alcohol intake. Within the low and normal alcohol intake groups subjects either continued their usual diet or reduced their caloric intake by 4,200-6,300 kJ/day (1,000-1,500 kcal/day) (with protein, fat, and carbohydrate provided as 15%, 30%, and 55% of total calories, respectively). Calorie reduction and alcohol restriction caused weight losses of 7.5 (p less than 0.001) and 2.1 (p less than 0.01) kg, respectively. Calorie reduction and alcohol restriction were associated with decreases in systolic blood pressure of 5.4 (p less than 0.001) and 4.8 (p less than 0.01) mm Hg, respectively, and in diastolic blood pressure of 4.2 (p less than 0.001) and 3.3 (p less than 0.01) mm Hg, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
Cardiovascular and plasma catecholamine responses to exercise in blacks and whites.
Authors: Walker A J , Bassett D R , Duey W J , Howley E T , Bond V , Torok D J , Mancuso P
Published: June 2012

The purpose of the present study was to assess possible racial differences in cardiovascular and plasma catecholamine responses to dynamic exercise. A biracial group of normotensive college-age men (15 blacks, 15 whites) were tested for maximal oxygen uptake, resting blood pressure, and heart rate. Subjects then rode a cycle ergometer at 25%, 50%, and 75% of peak oxygen uptake (6 minutes at each stage). Blood pressure and heart rate were measured during supine rest, seated rest, and at each stage of exercise with an automated blood pressure monitor. At each stage, venous blood was sampled to allow determination of plasma norepinephrine and epinephrine, and cardiac output was measured with the carbon dioxide rebreathing technique. The results indicated that resting blood pressure was similar for blacks and whites (114/68 versus 115/68 mm Hg, respectively). Blacks exhibited greater systolic and diastolic blood pressures during submaximal dynamic exercise. However, blacks also showed a trend toward a positive parental history of hypertension, which has been associated with an increased pressor response. Racial differences did not exist for heart rate or cardiac output, but blacks had higher values for total peripheral resistance both at rest and during exercise. Although no overall racial differences were seen for plasma catecholamine concentrations at rest, blacks had significantly lower levels of norepinephrine (1,275 versus 1,556 pg/ml) and higher levels of epinephrine (306 versus 216 pg/ml) than whites at the highest work rate. The current study confirms the increased pressor response to exercise in normotensive blacks. Blacks had an elevation in total peripheral resistance that was not accompanied by an increase in plasma norepinephrine levels.