bluuebunny/crossref_metadata_2025 huggingface dataset:
The endothelium partially obscures enhanced microvessel reactivity in DOCA hypertensive rats.
Authors: King C M , Webb R C
Published: June 2012

This study examined the contribution of the endothelium to pressor and depressor responses in the isolated, perfused mesentery of mineralocorticoid hypertensive rats. Following uninephrectomy, adult male rats were made hypertensive by subcutaneous implantation of deoxycorticosterone acetate (DOCA; 200 mg/kg); control rats were sham-treated. All rats received drinking water that contained 1.0% NaCl and 0.2% KCl. Following 4 to 6 weeks of treatment, the rats were anesthetized and the mesenteric vasculature was isolated and pump-perfused (constant flow with buffer) to evaluate changes in perfusion pressure. Vascular responses were determined before and after disruption of endothelial function by perfusion with oxygen free radicals generated in the buffer by electrical stimulation. Vasodilator responsiveness to acetylcholine and nitroprusside in the intact mesentery of hypertensive rats did not differ from that in the intact mesentery of normotensive rats, whereas pressor responses to norepinephrine in the intact mesentery of hypertensive rats were greater than normotensive values. Following disruption of endothelial function, depressor responses to acetylcholine were greatly attenuated whereas those to nitroprusside were unaltered or increased. Pressor responses to norepinephrine were potentiated in mesentery that had undergone endothelial disruption, and this potentiation was greater in hypertensive rats than in control rats. The slopes of pressure-flow curves in the presence of norepinephrine were less steep in mesentery with intact endothelium. The flow-modified component of these pressure-flow curves that was related to the endothelium was greater in mesenteric vascular beds of hypertensive rats. These results indicate that a factor released from the endothelium partially masks the enhanced vascular reactivity characteristic of this animal model of mineralocorticoid hypertension.
Analogue-specific action in vitro of atrial natriuretic factor on human red blood cell Ca2+-ATPase activity.
Authors: Davis F B , Blas S D , Davis M M , Davis P J
Published: June 2012

Specific atrial natriuretic factor (ANF) analogues have been found to have inhibitory activity in vitro in a calmodulin-dependent, human red blood cell membrane Ca2+-adenosine triphosphatase (ATPase) model. Studied at 10(-8) to 10(-6) M concentrations, atriopeptin I (residues 127-147 of rat prepro-ANF sequence) and atriopeptin III (residues 127-150) progressively inhibited Ca2+-ATPase activity by up to 20% (p less than 0.001). This degree of inhibition was consistent with activities of other (calmodulin-independent) enzyme inhibitors in this model. Therefore, the C-terminal Phe-Arg-Tyr sequence (residues 148-150) is unnecessary for atriopeptin action on Ca2+-ATPase. Human and rat atrial peptides with amino acids 123-150 were inactive, indicating that the 123-126 sequence (Ser-Leu-Arg-Arg) must be cleaved to activate atriopeptins in this system. Human ANF fragment 129-150 also had no effect on Ca2+-ATPase, defining the importance of residues 127-128 (Ser-Ser) proximal to the disulfide bridge (joining 129 to 145). The addition of purified calmodulin to red blood cell membranes in the presence of inhibitory ANF did not restore Ca2+-ATPase activity to normal levels, indicating that the ANF effect on this enzyme is calmodulin-independent. Atriopeptin I and atriopeptin III had no effect on red blood cell Na+, K+-ATPase activity in vitro. Thus, the structure-activity relationships of ANF analogues in this novel human cell membrane model are highly specific. Although the inhibitory action of ANF analogues on Ca2+-ATPase, a calcium pump-associated enzyme, may be unique to the red blood cell, the calcium dependence of the gluconeogenic effects of ANF in the kidney would be supported by inhibition of this ATPase.
Enhanced natriuretic effect of atrial natriuretic factor during mineralocorticoid escape in humans.
Authors: Gaillard C A , Koomans H A , Rabelink T J , Braam B , Boer P , Dorhout Mees E J
Published: June 2012

We examined the question of whether escape from the sodium-retaining effect of mineralocorticoid involves an increased natriuretic effect of atrial natriuretic factor (ANF). Seven healthy volunteers taking a 170 mmol Na/100 mmol K diet received an intravenous bolus (25 micrograms) followed by a 1-hour infusion (0.02 micrograms/kg/min) of ANF (human ANF-[99-126]) before and after 10 days of 9-fludrocortisone acetate, 0.5 mg b.i.d. Escape was accompanied by an increase in body weight (from 72.2 +/- 12.9 to 74.0 +/- 12.6 kg; p less than 0.05), mean arterial pressure (from 95 +/- 4 to 109 +/- 3 mm Hg; p less than 0.01), plasma ANF (from 9 +/- 2 to 24 +/- 4 pmol/L; p less than 0.01), and inulin clearance (from 124 +/- 9 to 137 +/- 7 ml/min; p less than 0.05). Indexes for renal sodium handling (lithium and free water clearance) were compatible with a decreased "proximal" and an increased "distal" tubular reabsorption fraction. ANF infusion raised inulin clearance comparably before and after escape to 138 +/- 10 and 152 +/- 7 ml/min, respectively, but the natriuretic effect was much larger (p less than 0.05) after escape (from 366 +/- 34 to 1294 +/- 278 mumol/min) than before (from 248 +/- 48 to 630 +/- 124 mumol/min). Indexes for tubular reabsorption were consistent with greater suppression of both "proximal" and "distal" tubular sodium reabsorption by ANF after versus before mineralocorticoid expansion. These results indicate that escape is accompanied not only by a rise in plasma ANF but also by potentiation of the natriuretic effect of ANF.(ABSTRACT TRUNCATED AT 250 WORDS)
Salt sensitivity in blacks. Salt intake and natriuretic substances.
Authors: Sowers J R , Zemel M B , Zemel P , Beck F W , Walsh M F , Zawada E T
Published: June 2012

Accumulating evidence suggests that hypertension in blacks is manifested in part by impaired renal excretion of salt. Consequently, this study was performed to determine if hypertensive and normotensive black subjects differ in their ability to generate known natriuretic substances. Fourteen normotensive and 11 hypertensive blacks were maintained on constant metabolic diets containing either 40 or 180 mmol of salt per day for 14 days each. During the last 4 days of each salt intake period, urine was collected for measurement of sodium, dopamine, and norepinephrine. On the last day of each 14-day dietary period, blood pressures were measured, blood was collected for measurement of plasma atrial natriuretic factor (ANF) and aldosterone, and urine was collected over 2 hours for measurement of prostaglandin E2 (PGE2). Both the normotensive and the hypertensive groups manifested salt sensitivity; their mean arterial pressure rose by 7 +/- 0.2 and 6 +/- 0.2%, respectively, when salt intake was increased from 40 to 180 mmol/day. The hypertensive group exhibited decreased (p less than 0.05) dopamine excretion as compared with the normotensive group for both dietary salt intakes. Plasma ANF levels increased (p less than 0.05) in the hypertensive group, but not in the normotensive group, with increasing dietary salt. Plasma aldosterone and urinary norepinephrine and PGE2 were comparable in the two groups for both dietary salt intakes. These data suggest that salt sensitivity is not unique to hypertensive blacks but occurs in normotensive blacks as well. Decreased renal production of dopamine may be a pathogenic factor in the development and maintenance of hypertension in blacks.
Acute sodium loading alters sodium pump in Caucasian hypertensive subjects.
Authors: Smith J B , Fineberg N S , Wade M B , Weinberger M H
Published: June 2012

The effect of an acute saline load on the sodium pump was determined from measurements of intracellular sodium and potassium, ouabain-inhibitable sodium efflux, and the number of sodium-potassium adenosine triphosphatase (Na,K-ATPase) sites per cell (using 3H-ouabain binding) of erythrocytes from 22 hypertensive and 21 normotensive subjects before and after a 2-1 infusion of 0.9% saline over a 4-hour period. Before the infusion, ouabain-inhibitable sodium efflux was the only measured parameter that was significantly (p less than 0.025) different between hypertensive (1.65 +/- 0.21 mmol/l red blood cell [RBC]/hr) and normotensive (1.46 +/- 0.25 mmol/l RBC/hr) subjects. After the saline infusion, there was a significant (p less than 0.001) decrease in the ouabain-sensitive sodium efflux of the hypertensive (1.55 +/- 0.22 mmol/l RBC/hr) but not of the normotensive (1.48 +/- 0.43 mmol/l RBC/hr) subjects. Although the changes in intracellular sodium of the normotensive and hypertensive subjects caused by the saline infusion were not significant, the fact that the change was in opposite directions in the two groups yielded a significant (p less than 0.02) differential response. After the saline infusion there was a significant increase in intracellular potassium (p less than 0.001, paired t test) and in the 3H-ouabain-binding affinity constant (p less than 0.001, paired t test) for both hypertensive and normotensive subjects. A second-order rate constant, which is an estimate of the apparent affinity constant of the sodium pump, was calculated from the ouabain-inhibitable sodium efflux, the intracellular sodium, and the number of Na,K-ATPase sites per cell.(ABSTRACT TRUNCATED AT 250 WORDS)
Thromboxane synthase inhibition enhances action of converting enzyme inhibitors.
Authors: Levens N R , Ksander G M , Zimmerman M B , Mullane K M
Published: June 2012

Mean arterial blood pressure was measured over a 24-hour period from the femoral artery of conscious, unrestrained spontaneously hypertensive rats. Oral administration of the angiotensin converting enzyme inhibitor CGS 16617 significantly lowered mean arterial pressure. In contrast, both the thromboxane synthase inhibitor CGS 12970 and the thromboxane receptor antagonist BM 13505 lacked an antihypertensive action in the spontaneously hypertensive rat. When administered concurrently, the thromboxane synthase inhibitor CGS 12970 potentiated the antihypertensive action of the angiotensin converting enzyme inhibitor CGS 16617. This effect was not observed with the thromboxane receptor antagonist BM 13505. In addition to CGS 16617, CGS 12970 also potentiated the hypotensive effect of two structurally dissimilar angiotensin converting enzyme inhibitors, benazapril HCL and captopril. Indomethacin blocked the thromboxane synthase inhibition-induced potentiation of the antihypertensive action of angiotensin converting enzyme inhibitors. The thromboxane synthase inhibitor CGS 12970 had no effect on the hypotension induced by hydralazine, indicating that the hypotension is not a nonspecific action related to the fall in blood pressure. These results may suggest that converting enzyme inhibition augments the levels and actions of a hormone that stimulates prostaglandin formation. It is well established that thromboxane synthase inhibitors eliminate the formation of the vasoconstrictor thromboxane A2 and allow reorientation of eicosanoid production toward the formation of vasodilating prostaglandins, which could enhance the antihypertensive action of angiotensin converting enzyme inhibitors.
Regenerative electrical activity and arterial contraction in hypertensive rats.
Authors: Lamb F S , Webb R C
Published: June 2012

Isolate tail arteries from spontaneously hypertensive rats-stroke prone strain (SHRSP) display oscillatory contractile responses to norepinephrine. These oscillations are not observed in tail arteries from normotensive Wistar-Kyoto rats (WKY). The mechanism underlying these oscillatory contractions was investigated by simultaneous measurement of isometric force development and membrane potential (Em) from tail artery strips in vitro. After equilibration in physiological salt solution containing 1.6 mM calcium (37 degrees C), resting Em was not different between WKY (-52 +/- 1.1 mV) and SHRSP (-52 +/- 0.4 mV). Norepinephrine (3 x 10(-7) M) produced a similar degree of depolarization in tissues from the two strains (WKY = (-42.5 +/- 0.9, SHRSP = -41 +/- 0.8). However, while Em recordings from WKY arteries were quiescent, those from SHRSP displayed bursts of electrical spiking activity that were temporally associated with the rising phase of oscillations in contractile force. The frequency and duration of these bursts of action potentials increased with the concentration of norepinephrine. Action potentials were not observed in calcium-free solution or in presence of nifedipine (3 x 10(-7) M). Releasing the passive stretch on the tissues caused a decrease in the rate of spiking. These studies demonstrate catecholamine-induced regenerative electrical activity in tail arteries from SHRSP that is dependent on extracellular calcium. This activity is unique to tail arteries from this strain.
Differential effect of dietary salt on renal growth in Dahl salt-sensitive and salt-resistant rats.
Authors: McCormick C P , Rauch A L , Buckalew V M
Published: June 2012

A high salt diet has been shown to increase renal mass of intact rats, although the mechanism by which this occurs has not been investigated. We used Dahl rats that are sensitive (DS) or resistant (DR) to the hypertensinogenic effect of salt to examine changes in renal size and composition caused by a high salt diet. Renal index, deoxyribonucleic acid (DNA), protein, water content, protein/DNA ratio, and cell number and size were measured in age-matched DR and DS on a high salt diet for 7, 14, or 28 days. The results were compared with those obtained from respective rats on a low salt diet. High salt diet elevated renal index and protein in DR and DS rats at each time point. After 7 days of a high salt diet, DNA increased in DS only. Protein/DNA ratio was progressively decreased by a high salt diet in DS and remained unchanged in DR rats. Cell number was increased 35% in DS versus only 13% in DR rats at 4 weeks. Cell size decreased 24% in DS and only 11% in DR rats. These results indicate that renal growth due to hyperplasia accompanies ingestion of a high salt diet in both DR and DS rats, but the rate of growth and the mechanism through which it occurs differ between strains. This difference may be important in delineating salt sensitivity and future development of hypertension.
Hyperparathyroidism and abnormal calcitriol metabolism in the spontaneously hypertensive rat.
Authors: Merke J , Lucas P A , Szabo A , Cournot-Witmer G , Mall G , Bouillon R , Drüeke T , Mann J , Ritz E
Published: June 2012

Abnormalities of calcium metabolism and of its two principal regulating hormones, parathyroid hormone and 1,25-dihydroxyvitamin D3 (calcitriol), have been reported in the spontaneously hypertensive rat (SHR). Reports of abnormal calcitriol metabolism in the SHR by several groups have not provided measurements of tissue calcitriol receptors. Similarly, few data are available as to the parathyroid status of the SHR. In the present study, circulating calcitriol levels and intestinal and parathyroid gland calcitriol receptor status were determined in male SHR and in Wistar-Kyoto (WKY) rats. Parathyroid status was investigated by determination of parathyroid gland mass together with tissue micromorphometry and by quantitative histology of bone as a measure of the biological action of parathyroid hormone. Circulating calcitriol levels were reduced in the 11-week-old SHR compared with the WKY rat (165 +/- 23 vs. 194 +/- 28 pmol/l, p less than 0.01, mean +/- SD). Calcitriol-free ratio was diminished and maximal specific binding capacity for calcitriol was increased in the SHR in parathyroid tissue (172 +/- 4.9 vs. 123 +/- 6.6 fmol/mg protein, p less than 0.01) and in intestinal mucosa with no change of receptor affinity. Plasma ionized calcium (1.29 +/- 0.05 vs. 1.45 +/- 0.35 mmol/l, p less than 0.05) and phosphate (1.5 +/- 0.26 vs. 2.4 +/- 0.03 mmol/l, p less than 0.05) were significantly lower in the SHR. Parathyroid gland mass was increased in the SHR (59 +/- 12 vs. 17 +/- 7 micrograms/100 g body wt, p less than 0.001) as a result of hyperplasia and not hypertrophy. Higher osteoclast numbers were observed in SHR bone (27.6 +/- 0.79 vs. 23.9 +/- 0.66 osteoclasts/mm2, p less than 0.01), suggesting increased parathyroid hormone activity. In summary, in the 11-week-old SHR we observed reduced circulating calcitriol levels together with increased tissue calcitriol receptor numbers, increased parathyroid gland mass, and histological evidence of hyperparathyroidism. It is possible that these abnormalities influence the development of hypertension in the SHR.
Sequential changes of cerebrospinal fluid sodium during the development of hypertension in Dahl rats.
Authors: Nakamura K , Cowley A W
Published: June 2012

The role of sodium retention and consequent changes in cerebrospinal fluid sodium concentration in the genesis of hypertension in Dahl rats was evaluated. Dahl salt-sensitive (DS, n = 7), Dahl salt-resistant (DR, n = 7), and Sprague-Dawley (n = 6) rats were housed in metabolic cages and instrumented with a stainless steel cannula in the cisterna magna and a femoral arterial catheter. A blood sample was drawn daily (200 microliters), and cerebrospinal fluid was collected by continuous 24-hour withdrawal (200 microliters/day). Daily sodium, potassium, and water balances were also determined. Rats were studied sequentially on 0.4%, 4%, and 8% sodium diets (7 days per sodium level). Mean arterial pressure increased with 4% NaCl from 107 to 120 mm Hg (p less than 0.05) over 24 hours in DS rats and remained at about that level until the NaCl was increased to 8%, which resulted in a gradual rise of mean arterial pressure over the next 7 days to 135 mm Hg. Cerebrospinal fluid sodium was unchanged in DR and Sprague-Dawley rats fed 4% or 8% sodium, but in DS rats rose from 152.3 to 155.2 +/- 0.6 meq/l on the third day at 4% sodium and remained elevated over the next 2 weeks of study. Blood sodium was unchanged throughout the study in all groups. On the first day only of the 4% and 8% sodium diets, both DS and DR rats exhibited a similar net retention of sodium, which was greater than the Sprague-Dawley rats (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
Chronic hypotensive effects of verapamil in angiotensin hypertension are steroid independent.
Authors: Lohmeier T E , Montani J P , Smith M J , Rushing E L
Published: June 2012

This study was designed to examine the mechanisms that contribute to the chronic hypotensive effects of verapamil during angiotensin II-induced hypertension. Hypertension was induced in five dogs by continuous intravenous infusion of angiotensin II (5 ng/kg/min) for 17 days. On the sixth day of angiotensin II infusion when daily sodium balance was achieved, mean arterial pressure (control, 92 +/- 4 mm Hg), plasma aldosterone concentration (control, 5.2 +/- 0.9 ng/dl), and renal resistance (control, 0.28 +/- 0.01 mm Hg/ml/min) were increased 37 +/- 8 mm Hg, 13.6 +/- 5.0 ng/dl, and 0.20 +/- 0.05 mm Hg/ml/min, respectively. At this time there were no significant changes in glomerular filtration rate, effective renal plasma flow, net sodium and water balance, or extracellular fluid volume. Subsequently, when verapamil was infused (at 2 micrograms/kg/min) simultaneously with angiotensin II (days 7-13), there was a net loss of 55 +/- 10 meq sodium, a 7.0 +/- 0.7% fall in extracellular fluid volume, and approximately a 70% reduction in the chronic effects of angiotensin II on mean arterial pressure and renal resistance; in contrast, verapamil failed to attenuate the long-term aldosterone response to angiotensin II. Further, although glomerular filtration rate and effective renal plasma flow tended to increase during verapamil administration, there were no consistent chronic long-term changes in these renal indexes. In comparison with these responses in hypertensive dogs, when verapamil was infused for 7 days before the induction of angiotensin II hypertension, there were no significant changes in any measurements except mean arterial pressure, which fell 11 +/- 1 mm Hg. Thus, these data fail to support the hypothesis that the chronic stimulatory actions of angiotensin II on aldosterone secretion are dependent on a sustained increase in transmembranal calcium influx. Moreover, these data indicate that the pronounced long-term hypotensive effects of verapamil in angiotensin II hypertension are due to impairment of the direct renal actions of angiotensin II rather than the indirect sodium-retaining effects that are mediated via aldosterone secretion.
Platelet calcium and quenched-flow aggregation kinetics in essential hypertension.
Authors: Taylor M A , Ayers C R , Gear A R
Published: June 2012

Abnormal platelet function may contribute to the complications of essential hypertension. We have studied the kinetics of platelet aggregation induced by adenosine diphosphate (ADP) or epinephrine, plasma beta-thromboglobulin, and basal, cytosolic, and free calcium, as correlates of platelet function. Fifteen untreated patients with essential hypertension and without detectable atherosclerosis, 18-40 years old, were compared with 30 matched normotensive control subjects. Maximal rates of platelet aggregation (Vmax) with ADP and epinephrine were significantly higher in patients than in control subjects (p less than 0.03), as assessed by quenched-flow aggregometry. However, significance was lost when Vmax was corrected for the platelet count. Paradoxically, the activation constants (Ka) for ADP were higher in patients than in control subjects (p less than 0.03). With ADP as the inducing agent, onset time (t) or lag period before aggregation begins was longer in patients than in control subjects (p less than 0.02). beta-thromboglobulin levels, an index of in vivo platelet activation, were not significantly different between the two groups (p = 0.13). The mean platelet cytosolic free calcium concentration was higher in patients (213 +/- 19 nM) than in control subjects (172 +/- 14 nM), but this difference was not statistically significant (p = 0.07). However, there was a close correlation between the free calcium level and systolic, diastolic, and mean blood pressure (p less than 0.003, p less than 0.04, p less than 0.004, respectively). No difference in platelet volume between the two groups was found. Our data suggest that platelets in the early stages of essential hypertension display an overall increased aggregation potential but a diminished sensitivity to ADP.(ABSTRACT TRUNCATED AT 250 WORDS)
How is the NaCl signal transmitted in NaCl-induced hypertension?
Authors: Lee J Y , Tobian L , Hanlon S , Hamer R , Johnson M A , Iwai J
Published: June 2012

Is the NaCl signal perceived as a small increase in the concentration of NaCl in extracellular fluid? We used 8 g NaCl/100 g soluble nutrients and fed only a hypertonic (1.4% NaCl) or a hypotonic (0.45% NaCl) drink to Dahl salt-sensitive (DS) rats. After 12 weeks, 11 rats receiving the hypertonic drink had a mean blood pressure of 195 mm Hg versus 195 mm Hg in 12 rats receiving the hypotonic drink. Thus, the high-NaCl signal seems unrelated to a higher NaCl concentration in extracellular fluid, thereby suggesting volume signals. Most volume controls are near the third brain ventricle (3V). As a working hypothesis, high dietary NaCl may swell the tissues surrounding 3V, which is slitlike. Such swelling would partially close the upper part of the slit and cause ependymal cells and nerve fibers on opposite walls to touch, possibly leading to hypertension in susceptible humans or rats. To test this, we stereotaxically blocked the aqueduct with inert silicone to produce hydrocephalus of 3V in DS rats and thus prevent ependymal cells and nerve fibers from touching. After blocking or sham-blocking the aqueduct, either a 6% NaCl diet or a 0.23% NaCl diet was started. Intra-arterial blood pressure was taken after 6 weeks. A group of 28 sham-blocked rats and a group of 29 blocked rats, all fed a 0.23% low NaCl diet, had equal blood pressures averaging 130 mm Hg.(ABSTRACT TRUNCATED AT 250 WORDS)
Hemodynamic effects of bufalin in the anesthetized dog.
Authors: Eliades D , Swindall B , Johnston J , Pamnani M , Haddy F
Published: June 2012

Studies in Lichstein's laboratory suggest that the endogenous digitalislike substance implicated in low renin hypertension might be a steroidal dienolide derivative. If this is true, the bufadienolides should block potassium vasodilation and enhance norepinephrine vasoconstriction, constrict blood vessels, raise blood pressure, and produce natriuresis and diuresis. We have therefore examined these parameters while infusing bufalin (aglycone), a bufadienolide, intrabrachially and intravenously in the anesthetized dog. Intrabrachial infusion of 5-25 micrograms/min with brachial arterial blood flow held constant at 100 ml/min produced a dose-dependent increase in perfusion pressure with rapid onset and offset, a progressive decrease in the vasodilator response to intrabrachial injection of 1 ml iso-osmotic potassium chloride solution (but not to acetylcholine), and an increase in the vasoconstrictor response to intrabrachial injection of 0.1 microgram norepinephrine. Intravenous infusion at 5-50 micrograms/min produced a dose-dependent increase in systemic arterial blood pressure, rate of change of ventricular pressure (dP/dt), and after the highest dose, cardiac irregularities. Natriuresis and diuresis were not observed. Thus, bufalin does in fact have some of the physiological properties required to be considered a candidate for the digitalislike substance found in low renin hypertension.
Red blood cell lithium-sodium countertransport in non-modulating essential hypertension.
Authors: Redgrave J , Canessa M , Gleason R , Hollenberg N K , Williams G H
Published: June 2012

Abnormalities in erythrocyte Li-Na countertransport have been reported in hypertensive subjects, and the available evidence favors familial aggregation and striking heritability of this marker. It is uncertain, however, whether the abnormalities are associated with hypertension per se or whether they may be concentrated in a particular subset of hypertensive subjects. In the present study, maximal rates of Li-Na countertransport were measured in red blood cells of 82 white subjects, including 37 normotensive subjects and 45 normal- or high-renin hypertensive subjects previously classified as non-modulators (n = 21) or modulators (n = 24). Mean countertransport activity was significantly higher in non-modulators compared with normally modulating hypertensive or normotensive subjects (0.475 +/- 0.044 vs. 0.309 +/- 0.028 or 0.249 +/- 0.012 mmol/l cell x hr, respectively, p less than 0.001). Modulators did not differ significantly from normotensive subjects with regard to mean countertransport activity. Red blood cell sodium pump and Na-K-Cl cotransport were not significantly different in modulating and non-modulating hypertensive subjects. These relations remained unchanged after adjusting for age, body weight, and plasma cholesterol levels by analysis of covariance. A countertransport value exceeding 0.50 mmol/l cell x hr occurred in 40% of the non-modulators but in only one of the other subjects. In contrast , while one half of the modulators and normotensive subjects had a countertransport value less than 0.235 mmol/l cell x hr, none of the non-modulators did. Thus, elevated countertransport appears to aggregate in the non-modulating subset of essential hypertensive subjects.(ABSTRACT TRUNCATED AT 250 WORDS)
Atrial natriuretic factor in Purkinje fibers of rabbit heart.
Authors: Anand-Srivastava M B , Thibault G , Sola C , Fon E , Ballak M , Charbonneau C , Haile-Meskel H , Garcia R , Genest J , Cantin M
Published: June 2012

The Purkinje fibers of the rabbit false tendons (chordae tendineae spuriae) are endocrine cells containing immunoreactive atrial natriuretic factor (ANF) and ANF messenger RNA (mRNA). These cells, as visualized by immunocryoultramicrotomy, contain immunoreactive ANF in their secretory granules and their Golgi complex and exhibit ANF mRNA, as visualized by in situ hybridization with an ANF complementary RNA probe. The content of immunoreactive ANF and ANF mRNA of the Purkinje fibers is midway between that of atrial and ventricular working cardiocytes. High-pressure liquid chromatography analysis of immunoreactive ANF using antibodies against the C-terminal and N-terminal moieties of the molecule indicates that part of immunoreactive ANF contained in Purkinje fibers is the propeptide [Asn1,Tyr126]ANF whereas part was nonspecifically cleaved into C-terminal and N-terminal ANF. The chordae tendineae spuriae exhibit binding sites for ANF (Kd:approximately 1.0 nM; Bmax:approximately 2.3 fmol/mg). ANF profoundly decreases basal and stimulated (epinephrine, dopamine, isoproterenol, and forskolin) adenylate cyclase activity and cyclic adenosine monophosphate (AMP) levels. ANF has little effect on norepinephrine-stimulated adenylate cyclase activity or on norepinephrine-stimulated cyclic AMP levels. ANF produces only a slight increase in guanylate cyclase activity and cyclic guanosine monophosphate levels at high (10(7)-10(6) M) concentrations. These results suggest an autocrine function for ANF in the modulation of the impulse in the peripheral conduction cells (Purkinje fibers) of the rabbit through changes in second messenger levels.
Agonist-induced vascular tone.
Authors: Nishimura J , Khalil R A , van Breemen C
Published: June 2012

The cellular mechanisms underlying the agonist-induced sustained contraction of the vascular smooth muscle are reviewed in the light of the use of Ca2+ and the change of Ca2+ sensitivity of the contractile apparatus. It is generally accepted that the main trigger for contraction of vascular smooth muscle is the elevation of intracellular Ca2+ concentration. However, the measurement of intracellular Ca2+ concentration during the sustained phase of agonist-induced contraction is reported to be lower than that of high K+ stimulation or the value obtained by the experiments with chemically skinned smooth muscle preparations. These observations indicate that a second regulatory system may exist. One possible mechanism is the effectiveness of Ca2+ use. Agonist-induced Ca2+ influx may be more effective in raising the intracellular Ca2+ in the bulk of the cytoplasm than is Ca2+ entry induced by depolarization by the inhibition of a putative sarcoplasmic reticulum buffer barrier. Another possibility is the change of Ca2+ sensitivity of the contractile apparatus. Although the survey of the recent literature concerning the phorbol ester-induced vasoconstriction tends to support a role for protein kinase C in the change of Ca2+ sensitivity of the contractile proteins, it fails to establish a clear link between receptors, protein kinase C, and myofilaments. By using new methods for permeabilizing smooth muscle fibers, which retain the function of receptors and signal transduction systems, we now provide direct evidence that the activation of G protein by norepinephrine or guanosine 5'-0-(3-triphosphate) (GTP-gamma-S), nonhydrolyzable GTP analogue, enhances myofilament sensitivity to Ca2+.
Leucine aminopeptidase M-induced reductions in blood pressure in spontaneously hypertensive rats.
Authors: Wright J W , Jensen L L , Cushing L L , Harding J W
Published: June 2012

Leucine aminopeptidase M significantly reduced blood pressure for up to 40 minutes when infused intracerebroventricularly into anesthetized spontaneously hypertensive rats (SHR) from a mean +/- SEM of 190 +/- 4 to 94 +/- 7 mm Hg and also in normotensive Wistar-Kyoto (WKY) rats from 138 +/- 5 to 68 +/- 8 mm Hg. Cerebrospinal fluid levels of angiotensin II (Ang II) and III were measured by radioimmunoassay and indicated drops with leucine aminopeptidase M infusion in SHR (from 36 +/- 6 to 11 +/- 1 pg/100 microliters) and in WKY rats (from 33 +/- 9 to 13 +/- 1 pg/100 microliters). Pretreatment with the specific angiotensin receptor antagonist [Sar1, Thr8]Ang II (sarthran) significantly diminished the subsequent leucine aminopeptidase M-induced decreases in blood pressure in SHR and facilitated recovery to base level blood pressure and heart rate in blood strains. Thus, exogenous application of leucine aminopeptidase M into the brain lateral ventricles of SHR is temporarily effective at reducing blood pressure, and this effect appears dependent on the brain angiotensinergic system. This treatment also reduced blood pressure in WKY rats; however, pretreatment with sarthran was reasonably ineffective at preventing subsequent leucine aminopeptidase M-induced decreases in blood pressure.
Bradykinin antagonism and prostaglandins in blood pressure regulation.
Authors: Mulinari R , Gavras I , Franco R , Gavras H
Published: June 2012

These experiments were designed to analyze the interaction of a bradykinin antagonist with prostaglandins in blood pressure regulation of normotensive rats. Male Wistar rats, divided into three groups, received a 5-minute intra-arterial infusion of the bradykinin antagonist [( DArgo-Hyp3-Thi5,8-DPhe7]BK-TFA) at 250 micrograms/min. Groups were either intact rats (group I, n = 5), pretreated with indomethacin (group II, n = 10), or pretreated with both indomethacin and prazosin (group III, n = 8). The bradykinin antagonist infusion, which was shown to inhibit exogenous bradykinin by greater than 76% in intact animals, did not alter mean arterial pressure in group I rats despite a twofold increase in norepinephrine and a threefold increase in epinephrine. Group II rats presented a progressive increase in mean arterial pressure during the bradykinin antagonist infusion (14 +/- 3 mm Hg), with no statistically significant change in plasma catecholamines. Group III, with lower baseline mean arterial pressure due to alpha 1-adrenergic blockade, had an increase in mean arterial pressure comparable with group II during bradykinin antagonist infusion (22 +/- 5 mm Hg), confirming that this response was not sympathetically mediated. We conclude that in normotensive rats bradykinin plays a role in blood pressure regulation that is closely linked to that of prostaglandins and that points to a balance between these systems.
Potentiation of renal effects of atrial natriuretic factor-(99-126) by SQ 29,072.
Authors: Seymour A A , Fennell S A , Swerdel J N
Published: June 2012

Depressor and renal activities of atrial natriuretic factor-(99-126) were determined in conscious, unrestrained spontaneously hypertensive rats treated with a neutral endopeptidase inhibitor, SQ 29,072 (7-[[2-(mercaptomethyl)-1-oxo-3-phenylpropyl]amino]heptanoic acid). SQ 29,072 (100 mumol/kg i.v.) prolonged the transient depressor effects of the peptide for as long as 2 hours. During the first hour after 3, 10, and 30 nmol/kg atrial natriuretic factor, urinary excretion of cyclic 3'5' guanosine monophosphate was significantly increased by 9.2 +/- 3.4, 13.0 +/- 2.2, and 12.7 +/- 4.2 nmol/kg/hr, respectively, in vehicle-treated rats and by 26.9 +/- 7.9, 52.1 +/- 11.1, and 46.4 +/- 12.2 nmol/kg/hr, respectively, in rats given 100 mumol/kg SQ 29,072. During the first hour after 3 and 10 nmol/kg atrial natriuretic factor-(99-126), the sodium loss was 161 +/- 56 and 139 +/- 42 mueq/kg/hr in vehicle-treated rats and was significantly greater (694 +/- 316 and 1,038 +/- 135 mueq/kg/hr) in rats given 100 mumol/kg SQ 29,072. After administration of 3, 10, and 30 mumol/kg SQ 29,072, the area over the curves of the depressor responses to 3 nmol/kg of the peptide increased from 297 +/- 70 to 306 +/- 108, 440 +/- 143, and 669 +/- 186 mm Hg.min, respectively, while the concurrent natriuretic responses rose from 161 +/- 56 to 250 +/- 88, 332 +/- 142, 464 +/- 164, and 694 +/- 316 mueq/kg/hr. In summary, the neutral endopeptidase inhibitor SQ 29,072 increased the magnitudes and especially the durations of the depressor, natriuretic, and cyclic guanosine monophosphate responses to exogenous atrial natriuretic factor-(99-126) in conscious spontaneously hypertensive rats, presumably by inhibition of degradation of atrial natriuretic factor in vivo. In conclusion, neutral endopeptidase inhibition offers an important new technique for enhancement and prolongation of the biological lifetime of atrial natriuretic factor.
Renal nerve contribution to NaCl-exacerbated hypertension in spontaneously hypertensive rats.
Authors: Sripairojthikoon W , Oparil S , Wyss J M
Published: June 2012

Previous studies demonstrate that bilateral renal denervation enhances urinary sodium excretion and delays the onset of hypertension in young (7-week-old) spontaneously hypertensive rats (SHR) maintained on ordinary laboratory chow. We interpret these data as suggesting that increased renal nerve activity in this model contributes to hypertension by causing excess sodium retention. More recent studies show that dietary NaCl supplementation increases blood pressure and peripheral sympathetic nervous system activity in NaCl-sensitive SHR (SHR-S). The present study tests the hypothesis that the renal nerves contribute to the rise in arterial pressure caused by dietary NaCl supplementation in this model. SHR-S were fed a high (8%) or basal (1%) NaCl diet beginning at age 7 weeks. Bilateral renal denervation was carried out 2 weeks after the initiation of the diets, at which time systolic blood pressure was significantly higher in the high (compared with the basal) NaCl group. Systolic blood pressure was reduced slightly less in denervated SHR-S on the high (compared with basal) NaCl diet during the following 5 weeks. Renal denervation performed 1 week before initiation of the diets attenuated the subsequent development of hypertension equally in both groups. Both renal denervation and the high NaCl diet increased alpha 2-adrenergic receptor numbers in the kidney; renal denervation caused an approximately equal increase in alpha 2-adrenergic receptor binding in SHR-S on high and basal NaCl diets. The high NaCl diet increased plasma noradrenaline concentration, and renal denervation lowered mean arterial pressure but did not decrease circulating catecholamines in either diet group.(ABSTRACT TRUNCATED AT 250 WORDS)
Impact of race on treatment response and cardiovascular disease among hypertensives.
Authors: Ooi W L , Budner N S , Cohen H , Madhavan S , Alderman M H
Published: June 2012

To determine the effect of race on cardiovascular disease occurrence among treated hypertensive patients, the experience of 1,807 black and 2,962 white hypertensive patients who entered a union/management--sponsored, worksite-based treatment program (1973-1985), was evaluated. Participants had similar socioeconomic profiles, equal access to health benefits, and received standard treatment. Median duration of observation was 42 months. Blacks had 48, and whites 129, of the 177 morbid (strokes and heart attacks) or mortal cardiovascular disease outcomes. At baseline, blacks had more electrocardiographic abnormalities (32% vs. 19%, p less than 0.0001), lower mean cholesterol (218 vs. 230 mg%, p less than 0.001), smoked more (35% vs. 30%, p less than 0.001), and were less likely to be treated for hypertension before entering the program (53% vs. 58%, p less than 0.01) than whites. They were also more likely than whites to belong to unions employing less skilled workers (p less than 0.0001). Overall, all-cause mortality rates between the races were similar. However, total cardiovascular disease morbidity and mortality rates were 10.5 (whites) and 6.4 (blacks) per 1,000 person years (p less than 0.005); the difference was largely explained by higher myocardial infarction rates among older (55 years or older) white men (15.6 vs. 7.5, p less than 0.05). That advantage was not present amongst younger black persons. In fact, blacks lost more years of life before age 65 (102 vs. 64 years/1,000 persons, p less than 0.025).(ABSTRACT TRUNCATED AT 250 WORDS)
Modulation of aortic smooth muscle cell membrane potential by extracellular calcium.
Authors: Palant C E , Stern N , Meyer A , Tuck M L , Lee D B , Yanagawa N
Published: June 2012

Removal of extracellular calcium may result in depolarization of the resting cell membrane potential. This has been attributed to the stabilizing action of calcium on the ionic permeability of the cell membrane. It is unknown whether this phenomenon is exclusively mediated by extracellular calcium or through associated changes in intracellular calcium. To examine this, we exposed rat aortic smooth muscle cells in culture to different calcium concentrations and studied their effects on the resting membrane potential and intracellular calcium activity. The resting membrane potential was dependent on the extracellular potassium concentration. Exposure to reduced extracellular calcium concentrations (0.25 and 0.5 mM) caused a steep and reversible depolarization of the membrane potential, but intracellular calcium, measured with fura 2-AM, was not reduced below that measured in control conditions (1.8 mM). Atomic absorption spectrophotometric measurements did not indicate a measurable gain in cell sodium after reduction of extracellular calcium levels. We conclude that extracellular calcium controls the resting cell membrane potential of vascular smooth muscle through a mechanism that is independent of cytosolic Ca2+ activity.
Role of endogenous brain kinins in the cardiovascular response to intracerebroventricular melittin.
Authors: Yang X P , Carretero O A , Jacobsen G , Scicli A G
Published: June 2012

Intracerebroventricular infusion of the peptide melittin increases immunoreactive kinins in the cerebrospinal fluid of anesthetized dogs, probably secondary to activation of brain or cerebrospinal fluid kininogenases. Intracerebroventricular melittin also increases blood pressure and heart rate, possibly mediated by brain kinins, since intracerebroventricular bradykinin also increases blood pressure and heart rate. We tested whether the effects of centrally administered melittin on blood pressure and heart rate could be blocked by simultaneous infusion of a kinin receptor antagonist, [DArg0]Hyp3-Thi5,8[DPhe7]bradykinin, in normotensive awake rats. In the controls, intracerebroventricular infusion of kinin receptor antagonist given for 1 hour at a rate of 10 micrograms/hr blocked bradykinin-induced increases in blood pressure and heart rate by 80%. Basal blood pressure and heart rate were not affected by the kinin receptor antagonist alone. After a 30-minute infusion of melittin (8 micrograms/30 min), cerebrospinal fluid kininogenase activity (n = 17) rose from 0.13 +/- 0.05 to 0.43 +/- 0.1 ng/ml/min (p less than 0.02). Although cerebrospinal fluid kinins increased from below sensitivity (0.02 ng/ml, n = 12) to 0.19 +/- 0.1 ng/ml (n = 17), this change was due to drastic increases in three rats, whereas in 12 of them kinins were below sensitivity. Incubation of bradykinin (10 ng) with 0.1 ml rat cerebrospinal fluid for 5 minutes destroyed 70% of kinins, suggesting that rapid destruction may have made detection of increased CSF kinins difficult.(ABSTRACT TRUNCATED AT 250 WORDS)
Effect of chronic sodium loading on cardiovascular response in young blacks and whites.
Authors: Falkner B , Kushner H
Published: June 2012

The effect of long-term oral sodium loading on blood pressure and on stress-induced cardiovascular response was studied in normotensive and marginally hypertensive young adults. The 121 subjects, 18-23 years old, included 38 whites and 83 blacks. Blood pressure and heart rate response to the stress of mental arithmetic was measured before and after 14 days of sodium load, which consisted of 10 g NaCl/day added to the usual diet. A sodium-sensitive response to sodium load occurred in 18.4% of whites and 37.3% of blacks. Sodium-insensitive subjects had a higher rate of sodium excretion (p less than 0.001). Sodium-sensitive hypertensive subjects had a significantly greater weight gain (p less than 0.001). A significant correlation between blood pressure change and sodium excretion (r = -0.28, p less than 0.01) occurred in the sodium-sensitive group. The high sodium intake did not augment the blood pressure or heart rate response to the beta-adrenergic-mediated stimulus of mental arithmetic in the population when grouped by blood pressure, race, or sodium sensitivity. These results suggest that blood pressure increase in response to sodium load, particularly in blacks, is related to functional changes in peripheral vascular resistance.
Captopril reduces aortic and microvascular growth in hypertensive and normotensive rats.
Authors: Wang D H , Prewitt R L
Published: June 2012

This experiment was designed to investigate the effect of converting enzyme inhibition on functional and structural vascular alterations in one-kidney, one clip hypertensive rats and in normotensive rats. Starting 1 day before surgery, 100 mg/kg/day captopril was given chronically to half of the hypertensive and normotensive groups in their drinking water. With use of intravital microscopy in the cremaster muscle, arteriolar dimensions were measured 4 weeks later, both before and after topical application of 10(-3) M adenosine. Mean blood pressure was 124 +/- 4 mm Hg in control rats and 103 +/- 5 mm Hg in captopril-treated control rats (p less than 0.05). Mean blood pressure was significantly elevated to 183 +/- 5 mm Hg in captopril-treated one-kidney, one clip hypertensive rats and 193 +/- 5 mm Hg in one-kidney, one clip hypertensive rats. With use of histological techniques, a marked reduction of medial-intimal area of the abdominal aorta was found in captopril-treated control rats (24%), and hypertrophy of the aortic wall in one-kidney, one clip hypertensive rats was decreased 26% by captopril. Structural diameter reductions occurred in large arterioles of the captopril-treated control and hypertensive groups and the nontreated hypertensive group. In spite of a significant increase in wall-to-lumen ratio of first-order arterioles in all captopril-treated rats, captopril decreased cross-sectional wall area of these vessels 37% in hypertensive and 20% in control rats, respectively. Measured by stereological techniques, small arteriolar density decreased 30% in captopril-treated hypertensive rats and 17% in captopril-treated control rats. Therefore, smaller arteriolar lumens, decreased aortic and arteriolar cross-sectional wall area, and arteriolar rarefaction after converting enzyme inhibition, in spite of rising or falling blood pressure, are evidence that vascular growth was inhibited in vivo.
Evidence that atriopeptin is not a physiological regulator of sodium excretion.
Authors: Goetz K L
Published: June 2012

Although much experimental evidence is consistent with the concept that atrial natriuretic factor (atriopeptin) is an important physiological regulator of renal sodium excretion, this hypothesis remains unproven. Indeed, a rapidly expanding collection of experimental data appears to be more compatible with the opposite conclusion, namely that circulating atriopeptin exerts only a trivial effect on renal sodium excretion during normal day-to-day living conditions. In this review, the substantial evidence demonstrating that elevations of plasma atriopeptin from threefold to 13-fold produce only a slowly developing and relatively modest natriuresis is reassessed in light of recently published data indicating that the acute intake of food (the pathway by which essentially all sodium enters the body under normal living conditions) does not increase circulating atriopeptin. These considerations imply that atriopeptin does not contribute to the process that elicits a postprandial natriuresis, a process that presumably is of primary importance in the physiological regulation of sodium balance. In addition, consideration is given to a number of common physiological, experimental, and pathophysiological conditions in which circulating atriopeptin does not correlate with renal sodium excretion. This lack of correlation implies that atriopeptin is not an important regulator of sodium excretion in these situations.