bluuebunny/crossref_metadata_2025 huggingface dataset:
Control of renin release in isolated rat glomeruli.
Authors: Beierwaltes W H , Schryver S , Olson P S , Romero J C
Published: September 2013

Glomeruli were isolated from rat kidneys using a passive sieving technique to study the mechanisms of basal and beta-adrenergic stimulated renin release. Glomeruli were enclosed within glass chambers and continuously superfused with Krebs media, or modified Krebs as described below, at a rate of 0.3 ml/min. The chamber effluent was collected in 10-minute fractions and measured for renin concentration (ng angiotensin I (A-1 generated) by radioimmunoassay. Basal renin was approximately 3 ng AI/ml/hr. Beta-adrenergic stimulation with isoproterenol (ISO), 178 micron M, increased renin concentration threefold (11 +/- 2 ng AI). The beta-blocker propranolol at 12 micron M halved ISO-stimulated renin, and at 120 micron M eliminated it. Doubling Krebs sodium concentration (280 mM) had no effect upon basal or ISO-stimulated renin release. Pretreating rast with DOCA and a high salt diet significantly reduced basal and abolished ISO-stimulated renin release. Increasing Krebs calcium (10 mM) did not affect basal but abolished ISO-stimulated renin release. Calcium-free Krebs had no significant effects. Increasing Krebs potassium (50 mM) increased basal renin fourfold (14 ng AI) while the absolute increase from basal due to ISO remained the same (23 ng AI). These results suggest that basal renin and ISO-stimulated renin are released via different mechanisms.
Monoclonal antibodies binding renal renin.
Authors: Dzau V , Mudgett-Hunter M , Kapler G , Haber E
Published: September 2013

Somatic-cell fusion of normal antibody-producing spleen cells with cells from a plasmacytoma culture results in a culture of hybrid cells from which a monoclonal line may be selected. These lines are immortal and may be amplified as tumors in syngeneic animals to produce large quantities of antibodies characterized by molecular homogeneity. We report the application of this technique to the production of antibodies binding canine renin. Balb/c mice were immunized with pure canine renal renin and their spleen cells fused with the NS-1 myeloma line. In two separate fusions, nine clones of cells were isolated that bound canine renal renin but did not cross-react with a number of protein antigens tested. One of these antibodies cross-reacted with renins of several different species, including human renin. Binding inhibition studies carried out with one of these monoclonal antibodies demonstrated a dissociation constant for renin of 10(-7) M. These monoclonal antibodies have great potential in answering significant questions concerning the structure, biosynthesis, tissue localization, and physiologic actions of renin.
Malignant hypertension: a syndrome associated with low plasma kininogen and kinin potentiating factor.
Authors: Almeida F A , Stella R C , Voos A , Ajzen H , Ribeiro A B
Published: September 2013

Plasma levels of kininogen, kallikrein, and prekallikrein were determined in patients with malignant hypertension (MH) and compared to normotensive controls (NC) and patients with mild to moderate essential hypertension (EH). Also, a recently described kinin potentiating factor (KPF) was estimated by dividing the value of kininogen determined by trypsin (Kgn-Try) by that of kininogen determined by human urinary kallikrein (Kgn-HuUk). No significant alterations were detected among plasma values of pre-kallikrein and kallikrein of MH as compared to NC. However, Kgn-HuUK values were significantly lower in MH (1.9 +/- 0.3 micron gLBK/ml) as compared to EH and NC (2.7 +/- 0.1 micron gLBK/ml and 3.0 +/- 0.2 micron gLBK/ml respectively, p less than 0.05). Furthermore, KPF values were also low (p less than 0.05) in MH (1.6 +/- 0.3) when compared with similar values obtained in EH and NC (3.0 +/- 0.2 and 2.8 +/- 0.1, respectively). Adequate control of blood pressure levels for 90 days in MH group caused no significant alterations in plasma levels of kininogen and KPF. It is suggested that diminished kininogen levels as well as a decrease in a kinin potentiation KPF that is generated in plasma by trypsin may be involved in the pathogenesis of human malignant hypertension.
Effect of renal nerve stimulation on urine and tissue kininogenase activity in cats.
Authors: Albertini R , de Guevara R L , Asenjo F , Boric M
Published: September 2013

The effect of electrical stimulation of efferent renal nerves on urine and renal tissue kininogenase activity was studied in cats. Handling renal nerves before crushing produced a significant increase is mean blood pressure (BP) in intact animals. After crushing, stimulation of efferent fibers (15 V, 0.5 msec, and 25 Hz) by 15-second train duration and at 2.45-minute intervals did not alter the average renal blood flow (RBF) or BP over 30 minutes. Glomerular filtration rate, water, and potassium excretion rates did not change significantly in either kidney. Sodium excretion in the ipsilateral kidney decreased significantly (p less than 0.05) in both intact and adrenalectomized cats. In intact animals, the kininogenase activity of urine (UK) also decreased significantly in both kidneys during nerve stimulation. In adrenalectomized animals it decreased significantly (p less than 0.05) only in the ipsilateral kidney, and UK of the ipsilateral kidney was significantly lower than in the contralateral (p less than 0.05). In both groups of cats, UK returned to control values during the recovery period of 30 minutes after stimulation. Adrenergic blockade abolished the effect of nerves stimulation on sodium and UK. Renal tissue kininogenase activity (RK) per gram of wet tissue was significantly lower in adrenergically blocked animals. No differences were detected when comparing RK content of ipsilateral vs a release of adrenal and peripheral nerve ending catecholamines.
Kallikrein and prekallikrein on the basolateral membrane of rat kidney tubules.
Authors: Yamada K , Schulz W W , Page D S , Erdös E G
Published: September 2013

Basolateral membrane (BLM) enriched fraction was isolated from homogenized rat kidney cortex by differential centrifugation. We also obtained a fraction enriched in plasma membrane (PM). The morphology of the isolated BLM fragments was studied by transmission and freeze fracture electron microscopy. The relative specific activity of Na+-K+-ATPase was enriched 7-fold, while that of marker enzymes for PM, endoplasmic reticulum, and lysosomes was lower than in the crude homogenate. There was a 10-fold difference in the ratios of activities of Na+-k+-ATPase to Mg2+-ATPase in the BLM and in the PM enriched fractions. Kallikrein activity was determined with S-2266 substrate and by radioimmunoassay of kinin released. It was low in the BLM fraction prior to adding detergent, but Triton X-100 increased the activity 12 to 16-fold. Both free trypsin and Sepharose 4B-bound insoluble trypsin increased kallikrein activity 2- to 3-fold in both the membrane-bound and soluble fractions, probably by activating a prekallikrein. The results were interpreted that the kallikrein studied originated from the distal tubular BLM.
Degranulation of renomedullary interstitial cells during reversal of hypertension.
Authors: Pitcock J A , Brown P S , Byers W , Brooks B , Muirhead E E
Published: September 2013

It was demonstrated earlier that the renal venous effluent of one-kidney, one clip hypertensive rats contained a vasodepressor lipid resembling the antihypertensive neutral renomedullary lipid (ANRL), following unclipping and as the arterial pressure (MAP) was lowered. Consequently, the sham-unclipped (clip-intact) and the unclipped kidney (CK and UCK) were studied by electronmicroscopy and morphometrically (Weibel's techniques). Renomedullary interstitial cells (RIC) of the CK had abundant granules. The collecting duct (CD) had tall lining cells containing pale granules and displayed intercellular channels. Following unclipping, the RIC degranulated and the CD cells became flattened, lost their pale granules, and the intercellular channels disappeared as the MAP decreased. These changes were evident by EM appearance and volume density measurements. The renopapillary changes occurred as the kidney secreted the ANRL-like substance into the blood.
Possible mechanism of prostaglandin-induced renal vasoconstriction in the rat.
Authors: Schor N , Brenner B M
Published: September 2013

We studied the role of the renin-angiotensin system in the vasoconstrictor effect induced by prostaglandins (PG) on the renal microcirculation in 25 euvolemic Munich-Wistar rats. Infusions of subvasodepressor doses of PgE2 and PGI2 led to lower mean values for single nephron (SN) glomerular filtration rate (GFR), total kidney GFR, glomerular plasma flow rate, QA, and ultrafiltration coefficient (Kf) than were found in animals given vehicle alone (control group). On the other hand, the mean values for glomerular transcapillary hydraulic pressure difference, delta P, and total renal arteriolar resistance, RTA, tended to be higher in the experimental groups. The effects of PGI2 on the renal microcirculation were more pronounced than for PGE2. These increases in delta P and RTA and decreases in QA and Kf are typical of changes induced by angiotensin II (AII). To further explore this AII-like phenomenon, an infusion of saralasin, a competitive AII antagonist, was used. Indeed, when saralasin was infused together with either PGE 2 or PGI2 the previously noted effects on delta P, QA, RTA and Kf were largely abolished. Thus, saralasin transformed the renal action of PGE2 and PGI2 from vasoconstrictor (low QA, high RTA) to vasodilator (high QA and low RTA). Therefore, the effects of nonvasodepressor doses of PGE2 and PGI2 on the renal microcirculation appear to depend on an intermediate action of AII.
Importance of the renal nerves in the pathogenesis of experimental hypertension.
Authors: Winternitz S R , Oparil S
Published: September 2013

Anatomical studies have demonstrated sympathetic innervation of the renal arterioles, juxtaglomerular apparatus, and renal tubules. Physiologic studies of the effects of the renal efferent nerves on renin release and renal sodium handling indicate that they play an important role in body fluid homeostasis and cardiovascular regulation. In addition, evidence is accumulating that stimulation of intrarenal mechanoreceptors and chemoreceptors causes in increase in renal afferent nerve activity and that alterations in renal afferent nerve traffic are, in turn, associated with changes in blood pressure and in vasoconstrictor tone in the contralateral kidney. Further, recent studies have demonstrated functionally significant connections between renal afferent nerves and the central nervous system. Interruption of the renal sympathetic nerves has been shown to prevent or attenuate hypertension in a number of animal models, suggesting that the renal nerves have an important role in the pathogenesis of experimental hypertension. In the spontaneously hypertensive rate of the Okamoto strain (SHR) and the DOCA-NaCl rat, the delay in the development of hypertension produced by renal denervation is due in part to increased sodium excretion thought to be secondary to interruption of the renal efferent nerves. In contrast, in one-kidney, one clip and two-kidney, one clip Goldblatt hypertension in the rat and coarctation hypertension in the dog, the depressor effect of renal denervation is unrelated to changes in urinary sodium excretion or plasma renin activity. In these models the attenuation of hypertension following renal denervation appears to be secondary to a decrease in peripheral sympathetic activity. Evidence in the one-kidney model suggests that interruption of the renal afferent nerves lower blood pressure via an effect on central noradrenergic mechanisms.
Plasma and platelet vasopressin in essential hypertension and congestive heart failure.
Authors: Preibisz J J , Sealey J E , Laragh J H , Cody R J , Weksler B B
Published: September 2013

In this study we found that, in 31 normal subjects, close to 90% of circulating arginine vasopressin (AVP), measured by radioimmunoassay, was associated with platelets. By using routine methods of centrifugation, which do not completely separate platelets, the normal range of plasma vasopressin was higher by twofold than the normal range in platelet-free plasma prepared by differential centrifugation, which was 1.4 +/- 1.0 sd pg/ml. Platelet vasopressin was 12.9 +/- 5.7 pg/ml. Patients with congestive heart failure had, on average, an elevated platelet-free plasma AVP, as did two patients with thrombocytopenia and one with thrombocytosis. Patients with essential hypertension had slightly high levels of platelet-free plasma AVP and demonstrated an abnormal inverse relationship between platelet-free plasma AVP and serum osmolality. Immunoreactive platelet vasopressin was slightly low in patients with essential hypertension and was subnormal in patients with congestive heart failure. These studies demonstrate that platelets normally present in centrifuged plasma cause an overestimation of the plasma vasopressin levels. Until the physiological meaning of plasma and platelet-bound AVP is understood, studies of circulating vasopressin should probably assess both plasma and platelet AVP levels.
Hemodynamic mechanism of blood pressure response to captopril in human malignant hypertension.
Authors: Saragoça M A , Homsi E , Ribeiro A B , Ferreira Filho S R , Ramos O L
Published: September 2013

The hemodynamic mechanism of blood pressure response to angiotensin blockade is well established in "benign" but not in human malignant hypertension. We studied the changes in mean arterial pressure (MAP), cardiac index (CI), pulmonary wedge pressure (PWP), and in plasma volume (PV) induced by a single oral dose of captopril (150 mg) in 11 patients with malignant hypertension. Two hours after captopril, MAP fell from 178.5 +/- 5.8 to 151.8 +/- 7.8 mm Hg (p less than 0.001) (means +/- SEM) due to a fall in total peripheral resistance (TPR) (from 54.8 +/- 6.8 to 46.4 +/- 1.6 arbitrary units, p less than 0.001). However, there was a simultaneous increase in CI (from 3.29 +/- 0.13 to 3.70 +/- 0.15 liter/min/m2, p less than 0.001), and a decrease in PWP (from 15.3 +/- 3.5 to 11.0 +/- 2.5 mm Hg, p less than 0.001), while PV remained unchanged (from 4.02 +/- 0.26 to 4.12 +/- 0.12 liters, n.s.). Our data show that, in human malignant hypertension, blood pressure response to captopril is due to a decrease in TPR, but in contrast to benign hypertension, there is also a simultaneous increase in CI. Our results suggest that, in malignant hypertension, potentially high CI levels are artificially normalized by the increased TPR and may be fully disclosed by vasodilation.
Atrial natriuretic factor. Characterization and partial purification.
Authors: Thibault G , Garcia R , Cantin M , Genest J
Published: September 2013

One of the main differences between atrial and ventricular cardiocytes is the presence in former of specific granules with morphological characteristics very similar to secretory granules found in peptide-secreting endocrine cells. It has been suggested that these granules are the storage place for the atrial natriuretic factor. In the rat, water deprivation produces an increase in atrial granularity but a significant decrease in acid-extractable diuretic and natriuretic activity, suggesting that the number of atrial specific granules does not necessarily represent natriuretic activity. The atrial natriuretic factor activity is destroyed by incubation with several proteases and does not inhibit the sodium-potassium ATPase, suggesting that the active substance is a small peptide that is probably different from the so-called natriuretic hormone. After a series of chromatographic steps in Sep-Pak cartridges, Bio-Gel P-10, CM Bio-Gel, and Mono S columns, the specific activity of the atrial natriuretic factor was increased from 193, corresponding to atrial homogenates, to 242,000, which corresponds to the last chromatographic step representing a 1250-fold purification. This material showed a potent natriuretic activity, as 10 picomoles increased natriuresis by 100%.
Comparison of beta-adrenoceptor blockers and calcium antagonists in hypertension.
Authors: Doyle A E
Published: September 2013

The calcium antagonist drug, verapamil, was compared in double-blind, double-dummy, crossover studies with two beta-adrenoceptor blocking drugs, pindolol and labetalol. All were equally effective as antihypertensive drugs in patients with mild-to-moderate hypertension. Verapamil caused a fall in blood pressure by reducing total peripheral resistance, as judged by echocardiographic studies, and had no adverse effects on airways resistance in patients with obstructive airways disease. The favorable hemodynamic effects and absence of serious side effects suggest that verapamil may be an important advance in the treatment of hypertension.
Pharmacokinetic and pharmacodynamic parameters in patients treated with nitrendipine.
Authors: Hansson L , Andrén L , Orö L , Ryman T
Published: September 2013

Nitrendipine (BAY e 5009) is a new calcium channel blocker with a marked effect on excitation-contraction coupling in different types of muscle cells. It has many similarities to the established agent, nifedipine. In the present study, nitrendipine was evaluated in a double-blind within-patient comparison. Twelve patients with essential hypertension were given nitrendipine 20 mg or 40 mg orally for three weeks following a 1-week placebo period. After a second 1-week placebo period, there was a crossover to the alternative dosage (20 or 40 mg respectively), and active therapy was again given for 3 weeks. Both doses of nitrendipine caused a significant and equal reduction of arterial pressure, which persisted for at least 24 hours. Only the highest dose caused an increase in heart rate. There were a few reports of headaches, flushing, and palpitation, particularly after the 40 mg dose. There was a significant correlation between the reduction of mean arterial pressure and the log plasma concentration (20 mg: r = -0.88, p less than 0.01; 40 mg: r = -0.94, p less than 0.001). There was a linear relationship between the area under the curve and the oral dose, indicating that liver enzyme saturation had not occurred. There was no accumulation of nitrendipine in plasma during 3 weeks of treatment.
Nifedipine in the long-term management of hypertensive heart disease.
Authors: Motz W , Strauer B E
Published: September 2013

Left ventricular (LV) hemodynamics, LV muscle mass, and LV geometry of 28 spontaneously hypertensive rats (SHR) treated for 20, 40, and 60 weeks with nifedipine (30 mg/kg/day) were compared with those of 29 age-matched untreated SHR. LV Pressure (PLV), systolic wall stress (Tsyst), ejection fraction (EF), cardiac index (CI), the ratio of LV muscle mass to body weight (LV/BW) and the ratio of LV muscle mass to end-diastolic volume (M/V) were determined. Myocardial contractility was analyzed through studies of the isolated LV papillary muscle. After 60 weeks of nifedipine treatment, PLV was 32.2% and Tsyst 22.9% lower in the treated group compared to the untreated control group (PLV 116 vs 171 mm Hg; Tsyst 165 vs 214 10(3)dyn/cm2). The degree of LV hypertrophy as indicated by LV/BW (-14%) and M/V (-21%) was less after treatment. LV pumping performance was considerably improved (EF = from 54% to 61%; Cl = from 175 to 220 ml/kg), whereas myocardial contractility indices such as maximum isotonic shortening velocity and isometric tension development remained unchanged. Thus, nifedipine reduced cardiac hypertrophy and improved LV function. These effects seem to result from a reduction in LV afterload.
Acute hypotensive response to nifedipine.
Authors: Magometschnigg D
Published: September 2013

Nifedipine, an effective hypotensive drug in severe hypertension, was investigated by invasive methods in 15 hypertensive patients while they were supine, erect, and exercising moderately. The effects of oral nifedipine 20 mg examined 45 minutes after the dose showed a reduced systemic arterial blood pressure via a reduction in peripheral resistance. Nifedipine reduced pulmonary arterial pressure and pulmonary wedge pressures (PWP) during exercise in patients with abnormally high values but did not alter them in patients with normal values. Heart rate and cardiac output increased by a reflex mechanism. The decreases in arterial blood pressure and PWP correlated with the initial values while the increases in heart rate and cardiac output did not correlate with the extent of blood pressure reduction. Since nifedipine decreases arterial blood pressure, pulmonary arterial pressure, and PWP in proportion to the pretreatment values, it is a useful drug in severe hypertension with and without elevated pulmonary pressures.
Does pharmacological profiling of a new drug in normotensive volunteers provide a useful guideline to antihypertensive therapy?
Authors: Brunner H R , Waeber B , Nussberger J
Published: September 2013

Similar pressor mechanisms should be active in hypertensive and normotensive subjects since hypertension is a quantitative rather than qualitative disorder. Consequently, if an antihypertensive drug is designed to specifically block a well-defined mechanism involved in blood pressure regulation, it should be possible to evaluate its efficacy rather precisely in normotensive volunteers before even administering the compound to a hypertensive patient. That this is indeed the case is illustrated by the example of angiotensin-converting-enzyme inhibitors. The magnitude of blockade that can be obtained in humans, the minimal does needed for maximal efficacy, and the onset and duration of action of the agents have all been precisely determined in normotensive volunteers. Subsequent administration to hypertensive patients merely confirmed these findings. Moreover, if the antihypertensive effect of converting-enzyme inhibitors could not be predicted in an individual hypertensive patient, this is not related to some unknown action of the drug that cannot be assessed in normal volunteers but rather to our lack of understanding of the precise mixture of pathogenetic mechanisms prevailing in any particular patient. Only the safety evaluation and the search for side-effects still has to be carried out in nonspecific fashion, thus requiring long-term observations in large numbers of patients. If the tolerance of new converting-enzyme inhibitors were more predictable, the number of studies in hypertensive patients could be drastically reduced since the antihypertensive profile of any new converting-enzyme inhibitor can probably be precisely determined in normotensive volunteers.
Influence of an angiotensin converting-enzyme inhibitor on diuretic-induced metabolic effects in hypertension.
Authors: Weinberger M H
Published: September 2013

Diuretic therapy is frequently accompanied by undesirable biochemical changes and side-effects. Two multicenter trials compared the effects of captopril combined with a diuretic to the administration of either agent alone in mild-to-moderate hypertensives. In addition to blood pressure, effects on serum potassium, uric acid, glucose, and cholesterol were examined. The first study (Study A) was conducted on 210 such patients randomly assigned to receive: 1) hydrochlorothiazide (H) 15 mg three times daily (t.i.d.); 2) captopril (C) 25 mg t.i.d.; or 3) C + H for 6 weeks. The second study (Study B) involved 415 patients randomly assigned to receive: 1) C 25 mg twice daily (b.i.d.) + H 25 mg b.i.d.; 2) C 50 mg b.i.d. + H 25 mg b.i.d.; 3) C 50 mg b.i.d. + placebo b.i.d.; 4) placebo b.i.d. + H 25 mg b.i.d.; or 5) placebo b.i.d. + placebo b.i.d. for 6 weeks. In both Studies A and B, all patients except those receiving placebo only (Study B-5) had significant (p less than 0.05) blood pressure reductions. In Study A, the combination of C + H (A-3) produced a significantly greater (p less than 0.001) reduction in blood pressure than either agent alone. In Study B, both C + H groups (B-1, B-2) had a significantly greater (p less than 0.01) blood pressure reduction than that seen with C alone (B-3). In Study A, those treated with H alone (A-1) had a significant (p less than 0.05) reduction in serum potassium and increases in uric acid, glucose, and cholesterol when compared to C alone (A-2) where no changes in these parameters were observed.(ABSTRACT TRUNCATED AT 250 WORDS)
How much can blood pressure be lowered?
Authors: Menard J , Chatellier G , Degoulet P , Plouin P F , Corvol P
Published: September 2013

Whatever the therapeutic goal proposed for diastolic blood pressure in hypertensive patients, the actual results of treatment in various health care delivery systems throughout the world are not as good as generally assumed. In the two recent controlled therapeutic trials, 24.5% (Australian trial) and 29.9% (Hypertension Detection and Follow-up Program) of actively treated patients had diastolic blood pressure levels above 90 mm Hg. In three British hospital clinics, diastolic blood pressure was greater than 90 mm Hg in 69% of the treated patients after 6 months to 1 year of treatment. In our own clinic, the blood pressure of 947 hypertensive patients registered in the Artemis system (Paris) between 1976 to 1980 decreased after 2 years on medical treatment from 177/108 to 142/87 mm Hg. However 21.1% of the patients studied still had a diastolic blood pressure above 95 mm Hg. In the general population, the percentage of treated patients not attaining goal levels varies from 42.9% to 71%. Not only is it important to agree upon goals, but it is urgent to standardize methods for collecting and analyzing the results of antihypertensive treatments in various health care delivery systems, since high rates of therapeutic failures might be related to the physician's strategy, the patient's characteristics, the disease's particularities, and the limited efficacy and side-effects of presently available drugs.
Hemodynamic response: decrease in cardiac output vs reduction in vascular resistance.
Authors: Lund-Johansen P
Published: September 2013

From a hemodynamic point of view, an adequate response to antihypertensive therapy would be restoration of a normal circulatory system. In most patients with mild to moderate essential hypertension considered to need drug therapy, the cardinal hemodynamic disturbance is an increased total peripheral resistance (TPR) and a normal or reduced cardiac output (CO). During a 10- to 17-year follow-up of untreated hypertensives, a gradual increase in TPR, increase in MAP, and a decrease in CO and stroke volume (SV) were seen. Hemodynamic responses to chronic drug therapy were studied at rest and during exercise in 250 men with mild to moderate essential hypertension in WHO Stage I. A significant reduction in TPR was seen on thiazide diuretics, nifedipine and verapamil, but there was no increase of subnormal CO or SV. A greater normalization of central hemodynamics was achieved by prazosin, which induced a reduction in TPR and an increase in CO and SV, particularly during exercise. In contrast, beta-blocker therapy was associated with a chronic reduction in CO and heart rate (HR) and usually no reduction in TPRI below pretreatment values. The chronic CO reduction was associated with an increase in arteriovenous oxygen difference. In 14 patients with therapy-resistant hypertension, a marked increase in TPR was found. Captopril induced a reduction in TPR with rest and exercise, and also a reduction in cardiac output. Prolonged therapy for 5 years with beta-blockers did maintain blood pressure control, but with no further decrease in TPR.(ABSTRACT TRUNCATED AT 250 WORDS)
Structural factors: the vascular wall. Consequences of treatment.
Authors: Folkow B
Published: September 2013

Like all tissues, blood vessels readily adapt their structure upon sustained functional changes. For example, pressure increases soon induce a largely proportional wall (w) thickening, where arteries, veins, and true resistance vessels respond alike. The latter also show a modest structural narrowing of average inner radius (ri), where the increased w/ri ratio results in a geometrically based vascular hyperreactivity. In primary hypertension, this type of precapillary resistance vessel adaptation implies an important "upward structural autoregulation" of systemic resistance, which is thereby kept increased also when vascular smooth muscle activity is entirely normal. Further, the systemic vascular hyperreactivity introduces a positive feedback interaction with functional pressor influences. By this mechanism, even marginal increases in "functional drive" may, if only sustained, steadily enhance the structural w/ri increase until it dominates hemodynamics. Similar alterations of the renal preglomerular vessels cause an early upward resetting of the renal barostat function, while wall thickening of large arteries helps to reset the baroreflexes. Also, the capacitance vessels show some structural adaptation that reduces venous compliance and contributes to blood volume centralization. Due to this overall structural resetting of hypertensive cardiovascular systems, the pharmacological problem of normalizing blood pressure is not one of merely damping an increased vascular smooth muscle activity. The task is more formidable, because effector cell activity must be kept even subnormal, despite counterregulatory mechanisms. These mechanisms almost all have been redesigned to maintain the high pressure state, with the long-range goal that true regression toward normality should ultimately ensue.
Mood changes during captopril therapy for hypertension. A double-blind pilot study.
Authors: Callender J S , Hodsman G P , Hutcheson M J , Lever A F , Robertson J I
Published: September 2013

A small double-blind pilot study was carried out to assess whether captopril treatment in hypertension has a euphoriant effect. Eight patients were maintained on constant therapy of atenolol and bendrofluazide for at least 4 weeks before and throughout the study. Captopril 25 mg three times daily or matching placebo was administered double-blind for 6 weeks, with crossover to placebo or captopril from Weeks 7 to 12. Psychiatric assessment was made at Weeks 3, 6, 9, and 12. During the captopril phase, blood pressure was reduced, plasma angiotensin II lowered, and plasma renin raised. Mood was slightly, but significantly, lower during captopril administration; thus, there was no evidence of an euphoriant effect of captopril. This pilot trial also indicates the feasibility of the approach, and such studies of hypertensives under therapy should be usefully extended and refined.
Effects of frog-skin angiotensin II in amphibians.
Authors: Proto M C , Coviello A , Khosla M C , Bumpus F M
Published: September 2013

The role of frog-skin angiotensin II (AII) in amphibia was studied by comparing the sodium and water permeability effects of three angiotensins (AII): frog skin (Ala-Pro-Gly-[Ile3, Val5]-Ang II), human [( Asp1, Ile5]-AII), and Japanese goosefish [( Asn1-Val5]-AII). Frog-skin AII increased the short-circuit current (SCC) significantly after it was added to the dermal side of the isolated skin of the South American frogs, Leptodactylus chaquensis and ocellatus, and the toad, Bufo arenarum, in concentrations of 10(-6) M. In frogs, the effect was significant at 15 minutes and reached 45% over control after 2 1/2 hours. The effect cannot be achieved with concentrations lower than 10(-7) M. Since amiloride (10(-4) M) blocked the SCC response, and absence of chloride in the bathing fluid did not, the effect is probably dependent on sodium transport. Human AII (10(-6) M) produced a similar response in summer frogs that had been treated with 0.1% NaCl for 14 days. Goosefish AII was ineffective at similar concentrations, and none of the angiotensins modified SCC in the toad bladder. Hydrosmotic effects could be achieved with the three angiotensins, the response being dependent on seasonal and species factors but always considerably lower than that of the neurohypophyseal peptides. Vascular reactivity of the isolated frog hindlimbs was compared by dose-response curves. Potency ratios on a molar basis against frog-skin AII was 1.136 for human AII and 1.193 for goosefish AII. The results show that the effects of the angiotensins differ in both the response of SCC to frog-skin angiotensin and its higher vascular effects.
Glomerular hemodynamics in persistent renovascular hypertension in the rat.
Authors: Herrera-Acosta J , Gabbai F , Franco M , Tapia E , Linfa G , Díaz L , Campos J
Published: September 2013

We studied the glomerular hemodynamics and activity of the tubuloglomerular feedback system (TGFS) in Wistar rats with persistent hypertension 60 days after removal of the clipped kidney in the Goldblatt (two-kidney, one clip) hypertension model. Ten hypertensive rats (HBP) were compared with 12 normotensive ones (NBP). Micropuncture studies revealed that values for the single nephron glomerular filtration rate (SNGFR), glomerular plasma flow (QA), and afferent oncotic pressure (PAR.A) were similar in both groups, whereas glomerular capillary pressure (PGC) and effective filtration pressure (EFP) were higher in the HBP group (p less than 0.05). A slight but insignificant increase in afferent resistance was present in the HBP group. A positive correlation was found between mean arterial pressure and stop flow pressure (SFP) (r = 0.64, p less than 0.05) but not with SNGFR, suggesting a reduction in the ultrafiltration coefficient in hypertensive rats. This was further supported by studies of the activity of the TGFS, which demonstrated that interrupting flow to the macula densa was followed by a smaller increment in SNGFR in HBP, in spite of a similar rise in SFP. The mechanism responsible for decreasing glomerular permeability is unknown but could be related to structural changes in glomerular capillary or to an increase in intrarenal angiotensin II, as has been demonstrated previously in this model. It is suggested that these adaptations occurring in the kidney exposed to hypertension can contribute to the maintenance of elevated arterial pressure after removing the stenotic kidney.
Hypertension among female workers in São Paulo, Brazil. Predictors and joint effects.
Authors: Ribeiro M B
Published: September 2013

Previous analysis based on data derived from a prevalence study of hypertension among workers in different economic activities in the Greater Metropolitan Area of São Paulo, Brazil, have shown separate effects of biologic and social attributes on diastolic blood pressure levels (DBP). The present paper explores joint effects of sociodemographic, anthropometric, and behavioral characteristics on blood pressure levels. For that purpose, the Morgan-Sonquist procedure on interaction effects in the prediction of DBP levels was used. Six independent variables emerged as predictors: age, Quetelet index, occupation, schooling years, subsector of the economy, and smoking. Very young and lean women who were also smokers had the lowest mean DBP levels (66.1 mm Hg). Young, overweight women without college education showed intermediate levels (71.5 mm Hg). Highest levels were found among older women in production-linked occupations engaged in transportation and metallurgy activities (89.5 mm Hg). The study suggests that the potential role of work-related characteristics on blood pressure levels is greatest among older women.
Synthesis of nonmammalian angiotensins and their comparative pressor properties in dogfish shark, domestic chicken, and rat.
Authors: Khosla M C , Bumpus F M , Nishimura H , Opdyke D F , Coviello A
Published: September 2013

To understand how vertebrates utilize angiotensins during evolutionary development, we undertook studies to synthesize and/or characterize angiotensin-like peptides from nonmammalian species. The present paper describes the synthesis of [Asp1,Val5,Asn9] angiotensin I (bull frog, Rana catesbeiana) (I), [Asn1,Val5,His9] angiotensin I (Japanese goosefish, Lophius litulon) (II), [Asn1, Val5,Asn9] angiotensin I (chum salmon, Oncorhynchus keta) (III), and [Asn1, Val5,Tyr9] angiotensin I (related to native angiotensin in snake, Elaphe climocophora (IV). Pressor properties of these peptides were compared with the peptides isolated from other species and related synthetic analogs in one representative species from three distinct classes of vertebrates: 1) elasmobranchs: spiny dogfish shark; 2) birds: domestic chicken; and 3) mammals: rat. The effect of angiotensins on short circuit current (to compare sodium and water permeability) was studied by adding these on the dermal side of the isolated frog skin. In the rat pressor bioassays, the above peptides possessed, respectively, I, 87.8%; II, 51.5%; III, 65.2%; and IV, 60.3% pressor activity of [Ile5] angiotensin II, which was blocked with a converting-enzyme inhibitor, captopril. In the conscious dogfish shark, the percentage increase of blood pressure based on preinjection level (= 100) in the dorsal aortic pressure was 35% to 60% for [Asp1,Ile5,His9] angiotensin I (human) (3 micrograms/kg), [Asp1,Val5,Ser9] angiotensin I (chicken) (3 micrograms/kg), [Asp1,Ile5] angiotensin II (3.6 micrograms/kg), and [Asn1,Val5] angiotensin II (6 micrograms/kg). Likewise, a 30% to 35% increase in blood pressure was obtained with angiotensin III (3 micrograms/kg), [Ile8] angiotensin II (4.4 micrograms/kg), and [Sar1,Ile8] angiotensin II (9.1 micrograms/kg). [Sar1,Thr8] angiotensin II and [Ile8] angiotensin I did not produce a significant pressor response even at high dose-level (8 micrograms/kg).(ABSTRACT TRUNCATED AT 250 WORDS)
Angiotensin-converting enzyme, bradykinin, angiotensin, and cerebral vessel reactivity.
Authors: Whalley E T , Wahl M , Sampaio C A
Published: September 2013

Bradykinin (BK) produced concentration-related relaxations of cat middle cerebral arteries and was ineffective in cat basilar arteries. On rabbit basilar arteries, BK initially produced concentration-related relaxations; however, when repeated at 2-hour intervals, BK eventually produced pure contractile responses. After preincubation of the tissues with cycloheximide, BK produced reproducible relaxation responses. The angiotensin-converting enzyme inhibitors, SQ 14,225, BPP5a, and BPP9a, had no effect on the concentration-effect curves of BK, AII, or 5-HT with any of the preparations, but responses to AI were inhibited. These results suggest that, in these tissues, angiotensin-converting enzyme is important for conversion of AI to AII, but apparently not for the degradation of BK.
Prostacyclin (PGI2) synthesis in the vascular wall of rats with bilateral renal artery stenosis.
Authors: Morera S , Santoro F M , Rosón M I , de la Riva I J
Published: September 2013

The ability of vessels (rings of arteries and vena cava) to synthesize prostacyclin (PGI2) "in vitro" was analyzed in the initial (6-day) and chronic (6-week) phase of two-kidney, two clip hypertension. Male Wistar CHbb THOM rats were used. Tissues were incubated for two hours in Krebs solution containing 14C-arachidonic acid as exogenous substrate. Specimens (in benzene-ethanol 4:1 vol/vol) and the unlabeled standard solutions of arachidonic acid, 6-keto PGF1 alpha, PGF2 alpha, and PGE2, were spotted on silica gel-G plates for thin layer chromatography. Conversion of 14C-arachidonic acid to stable metabolite 6-keto PGF1 alpha was used as an index of PGI2 synthesis. Results shown: 1) PGI2 is the major PG synthesized by the rat artery wall; 2) PGI2 synthesis was increased 2.4 times in the initial 6-day period of development of renovascular hypertension (RH); 3) no changes in PGI2 production were observed in arteries during the chronic 6-week period of RH; 4) abdominal vena cava has little or no capacity to produce PGI2. As PGI2 is a potent vasodilator, higher production by arteries during the 6-day period suggests that prostacyclin could play a modulator role on peripheral resistance during the initial phase of renal hypertension.
Effect of furosemide on renal function in the stenotic and contralateral kidneys of patients with renovascular hypertension.
Authors: Ruilope L , Garcia-Robles R , Sancho-Rof J , Paya C , Rodicio J L , Strong C G , Knox F G , Romero J C
Published: September 2013

In a group of six patients diagnosed as having unilateral renovascular hypertension due to fibromuscular dysplasia, inulin glomerular filtration rate, (GFR) and PAH renal plasma flow, (RPF) clearances, urine flow (V), urine sodium (UVNa), potassium (UVK), urinary excretion of prostaglandin E2 (UVPGE2), thromboxane B2 (UVTxB2), and 6-keto prostaglandin F1 alpha (UVPGF1 alpha) were measured in each kidney before and after the i.v. administration of furosemide (20 mg). The basal values of GFR, RPF, UVNa, UVPGE2, UVTxB2, and UV6-keto-PGF1 alpha were lower (p less than 0.01) in the stenotic kidney. Furosemide increased RPF 11% and 50%, GFR 25% and 62%, and V 142% and 280% in the contralateral and stenotic kidney respectively. The increase of UVNa was similar in the two kidneys. In the stenotic kidney, both UVPGE2 and UV6-keto-PGF1 alpha increased significantly (p less than 0.01) with furosemide while UVTxB2 remained unchanged. Furosemide did not alter the rate of excretion of the three prostaglandins measured in the contralateral kidney. We conclude that furosemide significantly improves renal circulatory and excretory function of the stenotic kidney. Since prostaglandin excretions also increased, the vasodilatation in the stenotic kidney may be prostaglandin mediated.
Effects of cyclooxygenase inhibitors on plasma and urinary kallikrein.
Authors: Schor N , Voos A , Stella R C , Ribeiro A B , Ramos O L
Published: September 2013

In vitro studies were performed to investigate the direct effects of the cyclooxygenase inhibitors (COI), meclofenamate, imidazol, acetylsalicylic acid (ASA), indomethacin, and acetaminophen on the plasma kallikrein system and on urinary kallikrein excretion. Biological (guinea pig ileum) and colorimetric (synthetic substrate) methods were used. Results showed that all COIs except ASA affected both the activation of pre-kallikrein in plasma and the direct activity of plasma kallikrein, but none of the COIs tested was able to alter the urinary kallikrein excretion. Additionally, in Wistar rats we studied the effects of chronic administration of ASA, meclofenamate, and indomethacin on the plasma kallikrein system and urinary kallikrein excretion. In contrast to the in vitro studies, administration of these COIs reduced the amount of total 24-hour urinary kallikrein excretion. Moreover, the pre-plasma kallikrein and total plasma kallikrein levels were diminished in all experimental groups. However, only ASA and meclofenamate increased the free-plasma kallikrein levels despite the fact the three COIs used reduced the high molecular weight kininogen. Thus, in vitro data suggest an important and direct effect of meclofenamate, imidazol, indomethacin, and acetaminophen on the plasma kallikrein system, without any effect on urinary secretion. ASA was the only COI that showed no direct effect in these experiments. Chronic COI administration in Wistar rats suggests that ASA, meclofenamate, and indomethacin affect both the plasma kallikrein-kinin system and kallikrein excretion. When these drugs are used to evaluate the interactions between prostaglandins and the kallikrein-kinin system, their possible effects through both mechanisms, directly or via prostaglandin inhibition, should be considered.
Antihypertensive polar and neutral renopapillary lipids. Which is a hormone?
Authors: Muirhead E E , Byers L W , Folkow B , Göthberg G , Thorén P , Brooks B
Published: September 2013

Two antihypertensive lipids can be derived from the renal papilla, the antihypertensive polar (APRL) and the antihypertensive neutral (ANRL) renomedullary lipid. The renal venous effluent of the unclipped kidney contains both ANRL and APRL. This effluent lowers the arterial pressure (AP) of the normal rat when infused i.v. As it lowers the AP the heart rate (HR) and sympathetic nerve activity (SNA) are depressed. ANRL infused i.v. also lowers HR and SNA as it depresses the AP. Conversely, APRL elevates HR and SNA as it lowers the AP. Thus, of the two lipids in the renal venous effluent after unclipping, ANRL appears to be dominant. APRL, however, in the renal venous effluent could potentiate the action of ANRL. The net effect of these observations is to support the view that ANRL is an antihypertensive hormone liberated by the kidney after unclipping. The renomedullary interstitial cells (RIC) degranulate after unclipping. ANRL can be derived from these cells. Thus, the RIC, cells known to exert an endocrine-type antihypertensive function, may well be the source of ANRL in the renal venous effluent after unclipping. The hormonal action of ANRL appears as a major cause of the lowering of the AP after unclipping. It is not known what factors modulate the RIC endocrine system. There is a suggestion that angiotensin may be one of these factors based on the ineffectiveness of these cells toward retarding hypertension when the circulating plasma angiotensin level is high, and their effectiveness when the circulating plasma angiotensin level is low.
Anteroventral third ventricle and renin-angiotensin system interaction in the two-kidney, one clip hypertensive rat.
Authors: Marson O , Saragoça M A , Ribeiro A B , Bossolan D , Tufik S , Ramos O L
Published: September 2013

To test the peripheral mechanisms of prevention and reversal of two-kidney, one clip (2K1C) hypertension in the rat by lesion of the anteroventral third ventricle (AV3V) region, we studied blood pressure responses in rats to AV3V lesion produced before (n = 8) or after (n = 8) clipping the left renal artery. Two groups of sham-lesioned, clipped rats (n = 9 each) served as controls. At the end of the experiments, saralasin and captopril were given to evaluate the angiotensin-dependent component of blood pressure. To study the influence of the procedures on plasma renin activity (PRA), two parallel groups of rats (n = 26 and 24, respectively) were submitted to similar surgical protocols. We observed that increases in blood pressure were significantly smaller in the previously lesioned compared to previously sham-lesioned animals (delta BP = 21.5 +/- 3.7 vs. 32.9 +/- 2.5 mm Hg, p less than 0.01); also, AV3V lesion almost completely reversed hypertension (BP from 167.5 +/- 2.9 to 136.0 +/- 4.1 mm Hg, p less than 0.001), which was not observed in the sham-lesioned animals (BP from 172.0 +/- 2.8 to 168 +/- 2.7 mm Hg, NS). Saralasin produced a significantly smaller decrease in BP in the lesioned animals compared to those with sham lesions during both prevention and reversal experiments. Similar results were observed with captopril. Previous AV3V lesion did not significantly affect PRA with clipping of the renal artery, but AV3V destruction after hypertension had been established resulted in significantly lower PRA compared to sham-lesioned animals (4.58 +/- 0.72 vs 8.38 +/- 1.79, respectively, p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)