bluuebunny/crossref_metadata_2025 huggingface dataset:
Dopamine surges in hyperadrenergic essential hypertension.
Authors: Kuchel O , Buu N T , Hamet P , Larochelle P , Bourque M , Genest J
Published: June 2012

From a total of 61 referred hypertensive patients, 21 were clinically suspected of pheochromocytoma but in none was this diagnosis confirmed. Instead we found nine of the 21 patients had surges of conjugated dopamine during hyperadrenergic periods unaccounted for by rise in norepinephrine (NE) or epinephrine (E). Overall, essential hypertensive (EH) patients had in plasma (ng/ml) higher conjugated dopamine (DA) (2.3 +/- 0.2 vs 1.0 +/- 0.1, p less than 0.01), increasing with age (p less than 0.01), lower conjugated NE + E (0.6 +/- 0.1 vs 1.2 +/- 0.2, p less than 0.01), and higher free E (p less than 0.007), lower urinary free DA and total DA but higher free NE + E excretions (each p less than 0.05) than 24 control subjects. Following the DA surges, a short-lived urinary overflow of total DA occurred. The patients with DA surges were older, had a higher incidence of low conjugated NE + E (less than 0.23 ng/ml), a higher proportion of arterial free DA, and higher venous baseline conjugated plasma DA than the rest of the patients. Patients with low conjugated NE + E had in turn higher plasma DA concentrations at several regional sampling sites than patients with normal conjugated NE + E. High conjugated DA in EH probably results from pulsatile DA surges leading to a rise of baseline plasma conjugated DA. In the short run DA pulses can result in temporary alpha- and beta-adrenergic actions of huge arterial free DA concentrations prior to DA conjugation; in the long run the excessive high affinity DA conjugation may take preference to the lower affinity NE and lowest affinity E conjugation and free E increases. Both result in an acute or chronic increase of sympathetic tone.
Behaviorally selective cardiovascular hyperreactivity in spontaneously hypertensive rats. Evidence for hypoemotionality and enhanced appetitive motivation.
Authors: LeDoux J E , Sakaguchi A , Reis D J
Published: June 2012

Spontaneously hypertensive rats (SHRs) and Wistar Kyoto controls (WKYs) were chronically instrumented for computer-assisted recording of arterial pressure (AP) and heart rate (HR) and examined during classically conditioned emotional (fear) reactions or during the performance of a repertoire of natural behaviors, including eating, drinking, grooming, exploring, and resting. The purpose of the study was to determine whether exaggerated cardiovascular reactivity in SHRs during aversive stimulation: 1) can be coupled to stimuli that before conditioning elicited negligible changes in AP and HR; 2) is accompanied by a proportionately enhanced level of emotional arousal; and 3) is specific to aversive emotional arousal or is also present during natural behaviors. The conditioned blood pressure response (in mm Hg) was greater (p less than 0.01) in SHRs (peak response, 20 +/- 3) than in WKYs (peak response, 7 +/- 1). While the conditioned pressure response was SHRs (peak response, 17 +/- 7 bpm). Behavioral tests indicated reduced emotional reactions in SHRs: SHRs showed less (p less than 0.05) drink suppression (75 +/- 17 sec) than WKYs (111 +/- 10 sec) and SHRs showed less (p less than 0.01) suppression of exploratory activity (201 +/- 40 sec) than WKYs (499 +/- 70) in the presence of the conditioned emotional stimulus. The magnitude of blood pressure changes (in mm Hg) above resting baseline was not different in SHRs and WKYs during eating (SHR, 32 +/- 3; WKY, 28 +/- 2), grooming (SHR, 17 +/- 3; WKY, 14 +/- 2), or exploring (SHR, 17 +/- 2; WKY, 18 +/- 2), but was greater (p less than 0.01) during drinking in SHRs (48 +/- 4) than in WKYs (32 +/- 2). The amount of time (sec) spent grooming (SHR, 55 +/- 23; WKY, 38 +/- 15) and exploring (SHR, 187 +/- 33; WKY, 165 +/- 42) did not differ between the strains, but SHRs spent more time (p less than 0.01) eating (SHR, 1103 +/- 88); WKY, 800 +/- 114) and drinking (SHR, 119 +/- 18; WKY, 32 +/- 12). These findings demonstrate that: 1) exaggerated cardiovascular reactivity in SHRs is readily coupled through conditioning to otherwise benign stimuli; 2) conditioned cardiovascular hyperreactivity is accompanied by a reduced not an enhanced level of conditioned emotional arousal; 3) cardiovascular hyperreactivity is not specific to aversive arousal but is nevertheless a behaviorally-specific mode of response; and 4) SHRs and WKYs differ in the performance of natural as well as emotional behaviors.
Plasma protein changes in primary hypertension in humans and rats.
Authors: Cloix J F , Devynck M A , Brentano J L , Meyer P
Published: June 2012

To determine whether plasma protein changes may be associated with primary hypertension, we analyzed plasma proteins from essential hypertensive (EHT) patients and genetically hypertensive rats using two-dimensional electrophoresis. An additional plasma protein, having a molecular weight of 13,000 daltons and an isoelectric point of 4.5, was found in 82% of the patients with borderline or moderate hypertension (n = 29) and in all permanently hypertensive patients (n = 12). This protein was detected in 36% of normotensive (NT) subjects (n = 50). In the latter, the influence of family history, sex, and secondary hypertension were studied. Plasma proteins were also studied in spontaneously hypertensive rats (SHR). In all plasma from young male (n = 10) and female (n = 6) SHR, two additional proteins (molecular weight = 16,000 daltons, pHi = 4.7 and 5.1) were detectable. These plasma proteins were not detectable in male Wistar Kyoto rats (WKY) and in 50% of female WKY, and their frequency was 10% (n = 10) and 0% (n = 3) in normal male WKY and in male WKY rendered hypertensive by methylprednisolone, respectively. We conclude that these alterations of plasma proteins may be considered a biochemical feature of primary hypertension.
Sympathetic contribution to the cardiac response to stress in hypertension.
Authors: Alicandri C , Fouad F M , Tarazi R C , Bravo E L , Greenstreet R L
Published: June 2012

Studies of cardiac performance in hypertension have often been restricted to cardiac output determinations, although the latter alone are inadequate for that purpose. To define the range of cardiac performance in hypertension, the response of left ventricular filling pressure to increased workload (static exercise) was determined in 39 subjects--eight normotensive (NT) volunteers, seven patients with borderline hypertension (BLH), and 24 essential hypertensives (EH), of age-matched groups. A rise of mean pulmonary wedge pressure (PWP) by 5 mm Hg or more during maximum handgrip (HG) was considered "abnormal" for a workload (SBP x HR x 10(-3)) increase of greater than or equal to 25%. All NT subjects and all patients with BLH as well as 16 of the 24 EH (EH-I) showed normal cardiac performance by this definition. In contrast, PWP increased greater than or equal to 5 mm Hg during HG in eight patients with EH (EH-II). The calculated increase in cardiac workload was not significantly different among the four groups (+5, 5.8, 5.4 and 5.5 respectively). Beta blockade (propranolol, 10 mg i.v.) slowed heart rate in all subjects and reduced SBP x HR product in all groups both at rest and during HG. Responses of PWP to HG were widely divergent in the different patients. However, as a group those patients with "impaired cardiac performance" before propranolol (EH-II) had a greater reduction in performance following propranolol than EH-I or NT. This study suggests that adrenergic support of cardiac performance might be important in some hypertensive patients with no evidence of heart failure.
Role of glandular kallikrein in the activation process of human plasma inactive renin.
Authors: Hiwada K , Matsumoto C , Kokubu T
Published: June 2012

Completely inactive renin was isolated from normal human plasma by DEAE-Sepharose column chromatography and Blue-Sepharose column chromatography. This inactive renin had a molecular weight of 54,000 daltons as determined by gel filtration on Ultrogel AcA 44. When the inactive renin was activated by trypsin, its molecular weight decreased to 48,000 daltons. The trypsin-activated renin differed from a native form of active renin in plasma with respect to molecular weight (active renin, 43,000), pI value (active renin, 5.20; trypsin-activated renin, 5.06), km value (active renin, 60 nmoles/liter; trypsin-activated renin, 89 nmoles/liter), Ki value for pepstatin A (active renin, 2.6 mumoles/liter; trypsin-activated renin 5.0 mumoles/liter) and pH profile for angiotensin formation. Glandular kallikrein (human urinary or pig pancreatic) did not activate the inactive renin. When the trypsin-activated renin was treated with glandular kallikrein, its activity was unchanged, but its molecular and kinetic properties except pI value (trypsin-activated kallikrein-treated renin, 4.82) coincided with those of a native form of active renin in plasma. These results indicate that glandular kallikrein does not directly activate inactive renin but participates in the activation process of inactive renin. The results also suggest that inactive renin in human plasma is a renin precursor.
Existence of prokallikrein in the kidney. Its biochemical properties compared to three active glandular kallikreins from the kidney, serum, and urine of the rat.
Authors: Nishimura K , Shimizu H , Kokubu T
Published: June 2012

Prokallikrein in the kidney was partially purified with immunoaffinity and DEAE Sephadex A-50 column chromatographies, and its biochemical properties were studied in comparison to three active glandular kallikreins purified from kidney, serum, and urine of the rat. The properties of the enzyme obtained by trypsin activation of prokallikrein were identical with those of active glandular kallikreins from the kidney, serum, and urine of the rat. Apparent molecular weights of prokallikrein, trypsin-activated kallikrein, active renal kallikrein, and glandular kallikrein in rat serum were 38,000 and of active urinary kallikrein, 37,000. Prokallikrein fraction was activated only by trypsin, but not by acidification, pepsin, and rat urinary esterase A treatments. Renal kallikrein, purified in the presence of soybean trypsin inhibitor (SBTI), contained 85% prokallikrein, but the enzymic fraction, purified in the absence of SBTI, contained 23% prokallikrein. Prokallikrein contents of urinary kallikrein and glandular kallikrein in rat serum were 16% and 20% respectively. These results suggest that prokallikrein is produced in the kidney and activated easily by a trypsin-like enzyme. Since rat serum contains active glandular kallikrein, kallikrein in the kidney may be secreted not only into the urine, but also into the blood.
Effects of captopril and enalapril on regional vascular resistance and reactivity in spontaneously hypertensive rats.
Authors: Richer C , Doussau M P , Giudicelli J F
Published: June 2012

The present study compares the effects of short-term treatments with captopril and enalapril, administered in equipotent antihypertensive doses, on the regional vascular resistances and on the regional vascular responsiveness to vasopressor agents of adult spontaneously hypertensive rats (SHRs). Three groups of animals were treated by gavage with captopril (100 mg/kg), enalapril (25 mg/kg), or distilled water for 8 days. Arterial blood pressure (BP), heart rate (HR), plasma renin concentration (PRC), and plasma converting-enzyme activity (CEA) were measured. Cardiac index (CI), total peripheral resistance (PR), and organ flow distribution were determined using microspheres. Renal and mesenteric vascular responsiveness to vasopressor agents was evaluated by continuous measurement of renal and mesenteric blood flows with miniaturized pulsed Doppler flow probes. Data showed that in the anesthetized SHR the two drugs induced similar reductions in BP, PR, and HR, without affecting CI. They simultaneously produced a strong converting-enzyme inhibition as evidenced by the suppression of angiotensin I effects accompanied by a potentiation of angiotensin II responses, a reduction in CEA, and an increase in PRC. Organ flows were similarly and homogeneously increased, especially in the kidneys, in both treated groups. Norepinephrine (NE) vasoconstrictor responses were abolished in the mesenteric vascular bed by both drugs, but in the renal, NE responses although completely abolished by captopril were only partially reduced by enalapril. It thus appears that diminished vascular responsiveness to NE, especially in the case of captopril, is probably involved along with converting-enzyme inhibition in the antihypertensive action of converting enzyme inhibitors (CEI), the mechanism of the difference between captopril and enalapril remaining still speculative.
Norepinephrine-induced potentiation of arginine vasopressin reactivity in arterioles of the spontaneously hypertensive rat.
Authors: Sueta C A , Hutchins P M , Dusseau J W
Published: June 2012

We have studied microvascular reactivity to vasopressin alone and in combination with norepinephrine in young (6- to 8-week-old) spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) controls. Closed-circuit TV microscopy was used to quantify the in vivo diameter responses of small arterioles (17 to 26 mu) to vasopressin (1.25 X 10(-8) to 3.75 X 10(-7) M) injected intraarterially alone and with simultaneous topical suffusion of a subthreshold concentration of norepinephrine in the cremaster muscle microcirculation. Percent decrease in luminal diameter was integrated over a 30-second period to obtain log concentration response curves. The vasoconstrictor response to vasopressin was concentration-dependent in both groups (p less than 0.001). A significant increase in reactivity to vasopressin alone was exhibited by the SHR arterioles compared to the WKY vessels (p less than 0.02). Maximum constriction was 55% higher in the SHR (p less than 0.04). The SHR also demonstrated a greater sensitivity to vasopressin (p less than 0.02). Vasopressin-induced vasoconstriction was potentiated by norepinephrine in the SHR, demonstrated by the significant shift of the curve up and to the left of the SHR response curve to vasopressin alone (p less than 0.01). The maximum response was 38% greater (p less than 0.02). Sensitivity was significantly enhanced (p less than 0.01). Additionally, the presence of norepinephrine stimulated a three-fold greater incidence of complete closure. In contrast to SHR results, topical suffusion of norepinephrine did not significantly alter the reactivity of the WKY arterioles to vasopressin-induced constriction. Our results support a role for vasopressin as a potential vasoconstrictor in the developing stage of SHR hypertension which may be modulated by norepinephrine and thus contribute to the elevated total peripheral resistance observed.
Effects of subpressor doses of angiotensin II on renal hemodynamics in relation to blood pressure.
Authors: Ljungman S , Aurell M , Hartford M , Wikstrand J , Berglund G
Published: June 2012

The renal hemodynamic response to subpressor doses of angiotensin II (AII; 0.1 and 0.5 ng/min/kg) was investigated in untreated 49-year-old men (n = 50) representing a wide blood pressure range. Renal blood flow, renal vascular resistance (RVR), glomerular filtration rate (GFR), filtration fraction (FF), plasma renin activity (PRA), plasma AII, plasma aldosterone, and the urinary excretion of sodium and norepinephrine were studied. The higher the initial blood pressure the greater was the increase in RVR in response to AII infusion (p less than 0.002), indicating an increased renal vascular reactivity with increase in initial blood pressure. The AII infusion gave a significant rise in RVR in both the borderline and hypertensive group, but gave no increase in RVR in the normotensive group, implying an enhanced sensitivity of the renal vasculature in the borderline and hypertensive group. The increase in RVR was greater in the hypertensive than in the borderline group, i.e., the hypertensives had a steeper dose-response curve than the borderline group, which points to the presence of structural vascular changes in the renal vessels in the hypertensives. The increase in RVR in response to AII was positively correlated to sodium intake and plasma aldosterone concentration, indicating that these two factors might modulate the renal vascular reactivity. These factors could, however, only partly explain that RVR increased more the higher the initial blood pressure. Thus, the results indicate that there is an increased reactivity of the renal vascular bed to AII in essential hypertension. The increased reactivity seems to be mediated through an increased sensitivity of the renal vasculature to AII in mild essential hypertension and also through the presence of structural vascular changes in established hypertension. These factors may lead to a reduced excretion of sodium and water and may therefore be of importance in the development and progression of essential hypertension.
Intrarenal pressure and sodium excretion in hypertension of chronic glomerulonephritis in humans.
Authors: Willassen Y , Ofstad J
Published: June 2012

The relationship between the fractional excretion of filtered sodium (FENa) and the peritubular capillary physical factors (PCPF) in the hypertension (HT) of chronic glomerulonephritis (GN) was examined in hydropenia (C) and during sustained isotonic saline volume expansion (E; 3% net increase of body weight) in 32 GN patients (16 with HT), and compared with our previous findings in 20 normal individuals (NORM) and 19 patients with essential hypertension (EH). Fourteen GN patients (seven with HT) had a 75% reduction of glomerular filtration rate (GFR), the others (nine with HT) had normal or near normal GFR. The PCPF were estimated from the intrarenal venous (wedged) pressure (IRVP) and the calculated efferent arteriolar protein concentration (EAPC). In C, IRVP correlated to GFR (r = 0.682, p less than 0.001) and (FENa) (r = -0.357, p less than 0.05), but IRVP and EAPC were similar in HT and normotension at comparable levels of GFR. The increase of FENa during E (delta FENa) was exaggerated in all HT groups even at reduced levels of GRF, and could not be related to changes in renal hemodynamics or PCPF. delta FENa correlated with mean arterial pressure in C both in GN (r1 = 0.702, p less than 0.01) and in the combined NORM/EH group (r2 = 0.478, p less than 0.01), with r1 greater than r2 (p less than 0.005). The findings indicate that the pathogenesis of hypertension of chronic glomerulonephritis is independent of changes in the PCPF, and are compatible with the idea that humoral factors are the main mediators of the altered sodium excretion during saline volume expansion in the HT of both chronic GN and EH.
Efficacy of captopril in relieving congestive heart failure developing during management of hypertension. Case report.
Authors: McNay J L , Dole W P
Published: June 2012

A 20-year-old woman presented with malignant hypertension, pulmonary edema, anemia, and azotemia. Blood pressure was adequately controlled only after progressively more intensive drug regimens, finally including minoxidil, nadolol, and furosemide. On these drugs, the patient developed progressive left and right heart failure, anasarca, and malnutrition. The control of hypertension, heart failure, and fluid retention, was accomplished by administration of captopril and furosemide. Captopril is a logical alternative to vasodilators in refractory hypertension complicated by congestive heart failure.
Propranolol effects on hypertension and the arterial wall beyond the treatment period in turkeys.
Authors: Simpson C F , Taylor W J
Published: June 2012

To determine if the effects of propranolol on hypertension and the arterial wall persisted for a significant time after the medication was discontinued, various parameters were compared at 16 weeks in control turkeys (CC), in birds on the medication from 3 days to 16 weeks (PP), and in others that were treated only from 3 days to 10 weeks (PC). At 16 weeks, arterial blood pressure, maximum rate of pressure increase (dp/dt max), and aortic intimal hyperplasia were lowest in the PP group, intermediate in the PC birds, and highest in the CC turkeys. Likewise, the vascular wall constituted 61% of the radius of the coronary arteries in the CC group, but only 52% and 45% in the PC and PP groups, respectively. At 16 weeks, heart rate was lowest and aortic tensile strength highest in the group that was treated for the entire period, at the end of which the average plasma propranolol level was 97 ng/ml. At the same age, heart rate and aortic tensile strength were approximately the same in the CC and PC groups, and propranolol was not detectable in the plasma. It is concluded that the administration of propranolol to hypertensive turkeys early in life reduced blood pressure, aortic intimal hyperplasia, and arterial wall thickness and that these effects persisted to a significant degree for at least 6 weeks after the medication was discontinued. The higher aortic tensile strength that was produced by propranolol did not persist.
Circulatory pressure-volume relationship and cardiac output in DOCA-salt rats.
Authors: Yamamoto J , Goto Y , Nakai M , Ogino K , Ikeda M
Published: June 2012

We studied the total vascular pressure-volume relationship and cardiac output (CO) in conscious rats receiving DOCA-salt or sham treatment. The mean circulatory filling pressure (MCFP) was measured by briefly inflation an indwelling balloon in the right atrium, and the MCFP-blood volume (BV) relationship over +/- 10% of BV was determined by rapid blood infusion or withdrawal. CO was measured in separate experiments using Fick's principle. Arterial pressure-volume relationship was also determined in additional experiments on anesthetized rats. Compared with sham rats, the mean arterial pressure was unchanged at 1 week, increased at 2 weeks, and increased further thereafter in the DOCA-salt rats. The BV was unchanged at 1 week, expanded at 2 weeks, unchanged at 5 weeks, and contracted at 8 weeks. There were no significant changes in MCFP, total vascular compliance (the inverse of the slope), nor unstressed volume (extrapolated volume axis intercept) at 2, 5, and 8 weeks. Total vascular capacity, assessed as BV at MCFP of 7.6 mm Hg, increased at 2 weeks, was unchanged at 5 weeks, and decreased at 8 weeks. Arterial compliance decreased at 5 and 8 weeks. CO remained unaltered at 1, 2, 5, and 8 weeks. These results suggest that the altered total vascular capacity may serve to maintain a normal CO against a rising afterload in the conscious DOCA-salt hypertensive rats, and that the decreased total vascular capacity may be a secondary hemodynamic feature with progression of hypertension.
North Karelia (Finland) hypertension detection project. Five-year follow-up of hypertensive cohort.
Authors: Nissinen A , Tuomilehto J , Elo J , Alasoini A , Varvikko P , Puska P
Published: June 2012

A 5-year follow-up study of a random sample of middle-aged hypertensives indicated that the North Karelia (Finland) Hypertension Detection Project was effective in reducing blood pressure levels. This analysis indicated that the intensification of drug treatment caused marked blood pressure reduction in the community, especially among individuals with previously undetected cases of hypertension. Reduction of blood pressure levels among nontreated persons was observed in this study and may reflect in part the importance of both active case finding and follow-up including health education and preventive services. The community approach used in this study reached and brought under control most of those people who were undetected at the beginning of the study and most of the hypertensives. On the basis of the results, it is concluded that a well-organized hypertension control program can meet the challenge of hypertension care and benefit millions of people throughout the world.
Twenty-four-hour hemodynamic profile during treatment of essential hypertension by once-a-day nadolol.
Authors: Mancia G , Ferrari A , Pomidossi G , Parati G , Bertinieri G , Grassi G , Gregorini L , Zanchetti A
Published: June 2012

The effect of nadolol (N) on 24-hour blood pressure (BP) and heart rate (HR) values and on their variability was examined in ambulant patients with essential hypertension, using the Oxford method to obtain continuous intraarterial recording and a computer to have a beat-to-beat analysis of the data. The recording was carried out without treatment and after 10 days' administration of N once daily by mouth (dose range: 80-320 mg). After N, 24-hour BP and HR were reduced by 17 +/- 3% and 27 +/- 4% respectively as compared to before N, the effect being similar for both systolic and diastolic BP. The hypertension and bradycardia were significantly more marked during the day than during the night, neither showing any attenuation in the hours furthest from the administration of the drug. During N, there was a reduction in the 24-hour variation coefficient for HR but the reduction was limited to the longer term component of this phenomenon, the moment-to-moment variations remaining unaffected. The long- and short-term variation coefficients for BP were not modified under N. These findings suggest that N once a day can reduce BP for 24 hours in ambulant hypertensive patients. The lack of alteration in variability of BP and moment-to-moment HR suggests that the hypotension is achieved without interfering with the mechanisms involved in cardiovascular homeostasis.
Reduced ratio of active-to-total urinary kallikrein in essential hypertension.
Authors: Lieberthal W , Arbeit L , Oza N B , Bernard D B , Levinsky N G
Published: June 2012

Urinary kallikrein excretion was studied in 34 patients with mild, normal-renin, essential hypertension without evidence of target organ damage and in 23 normotensive controls, using assays that measure both active (kininogenase activity) and total (active plus inactive) kallikrein. There was no significant difference in either active or total kallikrein excretion between the two groups. However, the ratio of active-to-total enzyme was decreased in the hypertensives (0.83 +/- 0.03 units/micrograms) compared to the normotensives (1.00 +/- 0.05 units/micrograms) (p less than 0.002). The active-to-total ratio was inversely related to sodium excretion in both groups, indicating that the proportion of active to inactive enzyme increased in response to reduced sodium intake. We conclude that, although absolute excretion of active and total kallikrein is not decreased, enzyme activity per microgram of total kallikrein excreted is reduced in mild, normal-renin essential hypertension. This abnormality may be due to a defective enzyme, or to a reduced excretion of active relative to inactive kallikrein. The latter could result from the presence of a urinary kallikrein inhibitor or to reduced activation of a proenzyme.
Absence of renin-like activity in rat aorta and microvessels.
Authors: Fordis C M , Megorden J S , Ropchak T G , Keiser H R
Published: June 2012

Vascular renin-like activity was studied in the aortas and the cerebral microvessels of Sprague-Dawley rats and in the aortas of spontaneously hypertensive rats. Methods were employed to maximize detection of tissue renin and to simultaneously minimize contamination of that activity by either plasma renin or nonspecific proteases capable of angiotensin I generation. To this end, renin activity was measured near its pH optimum; plasma renin was eliminated by nephrectomy; and nonspecific proteases such as cathepsin D were either inhibited by proteolytic blockers or removed by chromatography over immobilized bovine hemoglobin. Aortic vascular renin-like activity was detected in rats not subjected to nephrectomy and could be inhibited by preincubation of samples with antimouse renin antibody shown to cross-react and inhibit rat plasma renin activity. Furthermore, vascular renin-like activity disappeared after nephrectomy in parallel with the disappearance of plasma renin activity. In the absence of contaminating enzymatic activities, no tissue renin-like activity could be demonstrated in either aortas or cerebral microvessels of Sprague-Dawley rats or in aortas of spontaneously hypertensive rats.
Sodium and potassium ion transport accelerations in erythrocytes of DOC, DOC-salt, two-kidney, one clip, and spontaneously hypertensive rats. Role of hypokalemia and cell volume.
Authors: Duhm J , Göbel B O , Beck F X
Published: June 2012

Sodium (Na+) and potassium (K+) transport by the furosemide-sensitive Na+-K+ transport system, the Na+-K+ pump, and the cation leak(s) were studied in erythrocytes from DOC-water, DOC-salt, two-kidney, one clip (Sprague-Dawley), and spontaneously hypertensive rats (Wistar-Kyoto). Rubidium (Rb+) was used as a tracer for K+. After 4 weeks of DOC-salt hypertension, inward K+ (Rb+) transport by the furosemide-sensitive system was increased threefold, and the inward Na+ leak and the red cell Na+ content were elevated by about 50%. The rise in cell Na+ accelerated K+ inward and Na+ outward transport by the Na+-K4 pump, DOC-water hypertension caused similar but less pronounced changes. In two-kidney, one clip hypertension, the Na+ leak and the Na+-K+ pump rates were slightly elevated, and furosemide-sensitive Rb+ uptake tended to be increased. In spontaneously hypertensive rats, furosemide-sensitive Rb+ uptake was accelerated by 50%. The marked hypokalemia in DOC-water and DOC-salt hypertension was associated with a slight loss of red cell K+ and an increase in mean cellular hemoglobin content (MCHC), indicative of cell shrinkage. Hypokalemia induced by dietary K+ deficiency caused alterations in red cell cation transport, content, and cell volume which were qualitatively similar but more pronounced than those seen in DOC-salt hypertension. Osmotic shrinkage in vitro induced a severalfold acceleration of furosemide-sensitive Rb+ uptake, similar to that observed in rat erythrocytes shrunken in vivo in K+-deficient states. It is concluded that the acceleration of furosemide-sensitive K+ (Rb+) transport in erythrocytes of mineralocorticoid hypertensive rats is largely caused by the hypokalemia and consecutive red cell K+ loss and shrinkage, respectively. Mean cellular hemoglobin content (MCHC) is thus a parameter that must be considered in studies on Na+ and K+ transport across the membrane of rat erythrocytes.
Atrial natriuretic factor: reduced cardiac content in spontaneously hypertensive rats.
Authors: Sonnenberg H , Milojevic S , Chong C K , Veress A T
Published: June 2012

We recently discovered a potent natriuretic factor in cardiac atrial tissue. The present experiments were designed to determine whether hypertension was associated with altered tissue content of this atrial natriuretic factor. Extracts were prepared using fresh atria from spontaneously hypertensive rats of the Okamoto strain and from their Wistar-Kyoto controls. Two groups of anesthetized, normovolemic rats (Sprague-Dawley) were used to measure the renal natriuretic and chloriuretic effect of each type of extract. Results indicate that atrial content of natriuretic factor is reduced in hypertensive rats compared to control animals. We speculate that chronic release of the factor could have depleted atrial stores, and that increased blood levels of atrial natriuretic factor may be involved in the generation and maintenance of hypertension in this model.
Inhibition of furosemide-induced increases in plasma renin activity by amiloride.
Authors: Shimoda K , Lee T C , Maxwell M H
Published: June 2012

The effect of the potassium-sparing diuretic, amiloride, was studied in conscious rabbits bearing chronic indwelling cannulas to assess whether its reported in vitro kallikrein-inhibiting activity may produce a suppressive effect on furosemide-induced renin secretion similar to that previously demonstrated with another kallikrein inhibitor, aprotinin. Furosemide elicited a rapid and persistent rise in plasma renin activity (PRA), but pretreatment of the same rabbits with a 15-minute intravenous infusion of amiloride, which amounted to 1 mg/kg and commenced at 30 minutes before furosemide, completely prevented this rise. Amiloride also prevented furosemide-induced kaliuresis without an attenuation of the diuretic or natriuretic response and did not alter plasma potassium concentration in the absence of any change in external potassium balance, indicating that suppression of the PRA response is due neither to prevention of extracellular fluid volume contraction nor to the known suppressive effect of hyperkalemia. Mean arterial pressure tended to fall slightly but not significantly with or without amiloride pretreatment. On the basis of these findings and those of our antecedent study with aprotinin, we conclude that the striking similarity between the suppressive effects of two dissimilar inhibitors of kallikrein on pharmacologically evoked renin secretion is consistent with the hypothesis that renal kallikrein participates in the mechanism of renin secretion in vivo.
Sympathetic nerves and adrenal medulla: contributions to cardiovascular-conditioned emotional responses in spontaneously hypertensive rats.
Authors: Sakaguchi A , LeDoux J E , Reis D J
Published: June 2012

This report investigates the contributions of the sympathetic nerves and adrenal medulla to resting mean arterial pressure (MAP) and to emotionally conditioned MAP and heart rate (HR) responses in unrestrained spontaneously hypertensive rats (SHR) and Wistar-Kyoto normotensive control rats (WKY). Resting MAP (in mm Hg), which was higher in SHR (WKY = 120 +/- 4; SHR = 163 +/- 4; p less than 0.01), did not differ in the two strains following chemosympathectomy (WKY = 105 +/- 2; SHR = 101 +/- 2; n.s.). Adrenal medullectomy did not affect resting MAP in WKY (125 +/- 6; n.s.) but lowered it in SHR (146 +/- 5; p less than 0.05), relative to controls (see above). The conditioned pressor response (in mm Hg) in controls consisted of two peaks (I, II) in both strains, but was exaggerated in SHR (I = WKY, 13 +/- 1; SHR, 25 +/- 2; p less than 0.01; II = WKY 10 +/- 2; SHR 20 +/- 2; p less than 0.01). Chemosympathectomy suppressed (relative to controls) the first peak, but not the second, in both strains (WKY: I = 4 +/- 1, p less than 0.01; II = 12 +/- 2, n.s.; SHR: I = 6 +/- 1, p less than 0.01; II = 15 +/- 2, n.s.). Adrenal medullectomy alone had little effect on the pressor response, but when combined with chemosympathectomy both peaks were largely eliminated (WKY: I = 2 +/- I; II = 5 +/- 1; SHR: I = 1 +/- 0; II = 2 +/- 0). These data indicate that: 1) hypertension in conscious, freely behaving SHR is largely sustained by the sympathetic vasomotor nerves but that the adrenal medulla contributes to the magnitude of the elevation; 2) the early component of the exaggerated pressor response during aversive stimulation is mediated by sympathetic vasomotor excitation; and 3) the later component of the exaggerated pressor response reflects coactivation of the sympathetic vasomotor nerves and the adrenal medulla.
Intestinal microvascular adaptation during maturation of spontaneously hypertensive rats.
Authors: Bohlen H G
Published: June 2012

Adaptive microvascular changes in increased arterial pressure were investigated in the intestine of spontaneously hypertensive rats (SHR). In 4- to 5-week-old normal Wistar-Kyoto (WKY) and SHR ras, as well as in 18- to 21-week-old WKY rats, the number of arterioles of a given type per milligram of tissue were very similar. However, 18- to 21-week-old SHR had 30% to 35% fewer arterioles in the diameter range of 25--35 mu, as if intestinal vessels were lost or failed to grow during maturation. The largest and smallest arterioles in the intestine of adult SHR were constricted by 20% to 25%, but other vessels in the SHR had an equal or increased diameter relative to those in WKY rats. As a result of rarefaction and selective vasoconstriction in SHR, microvascular pressures in the intestinal muscle of SHR were near those in WKY rats, and those in villi of SHR were equal to those in WKY rats despite a 60% to 70% increase in mean arterial pressure in SHR. The percentage of small arterioles (less than 15 mu) that were intermittently closed to flow at rest was minimal, and the total number of small vessels per milligram of tissue was equal in WKY and SH rats. These data indicate that the adaptive changes in the intestinal vasculature of SHR do not include the loss of small arterioles as occurs in skeletal muscle but that the vascular branching pattern is disturbed, and the largest and smallest arterioles are constricted in the intestine of SHR.
Role of cardiovascular receptors on the neural regulation of renin release in normal men.
Authors: Egan B M , Julius S , Cottier C , Osterziel K J , Ibsen H
Published: June 2012

Although factors influencing renin release have been studied extensively, one facet of renin release remains controversial, namely, neural regulation by arterial high-pressure receptors and cardiopulmonary low-pressure receptors. We therefore designed four studies to investigate systematically the separate and combined effects of unloading (decreased stretch) high- and low-pressure receptors on renin release in normal men. Selective unloading of cardiopulmonary receptors was induced by impeding the venous return with tourniquets around the thighs. A predominant unloading of arterial (carotid) baroreceptors was elicited with upright posture and simultaneously preventing the venous pooling in the legs. Unloading of both high- and low-pressure receptors was achieved by both upright standing and tilting. During postural experiments to predominantly unload arterial baroreceptors, the heart rate increased and the veins constricted, but renin failed to increase. The postural increase of renin occurred only if we allowed venous pooling in the legs. Selective unloading of cardiopulmonary receptors elicited substantial increases of renin. When both the cardiopulmonary and arterial baroreceptors were unloaded, renin increased more than with isolated unloading of cardiopulmonary receptors. We conclude that: 1) in intact humans it is possible to demonstrate an independent role of cardiopulmonary receptors in the control of renin release; 2) there Is evidence for interaction between the two receptor systems in renin control; but 3) an independent role for arterial baroreceptors in the control of renin release could not be demonstrated under the conditions of this experiment.
The effect of aprotinin (a serine protease inhibitor) on renal function and renin release.
Authors: Seto S , Kher V , Scicli A G , Beierwaltes W H , Carretero O A
Published: June 2012

We studied the effect of aprotinin, a reversible inhibitor of kallikrein and other serine proteases, upon urinary kallikrein and kinin excretion, renal function and hemodynamics, blood pressure, and plasma renin activity (PRA). When aprotinin was administered to anesthetized rats at 10,000 KIU/kg as a bolus, and at 1000 KIU/kg/min infusion for 60 minutes, urinary kininogenase activity and immunoreactive kallikrein, kinins, sodium, potassium, and water excretion, and PRA decreased significantly. Aprotinin also caused a 36% decrease (p less than 0.001) in renal blood flow (RBF), and a 37% decrease (p less than 0.001) in glomerular filtration rate (GFR), although neither blood pressure nor cardiac output changed. The effect of aprotinin on PRA was further studied in conscious rats before and after stimulation of renin release by isoproterenol or furosemide. Aprotinin (5,000 KIU/kg bolus and 1000 KIU/kg/min infusion for 60 minutes) did not alter basal or isoproterenol-stimulated PRA, but it blunted the increase in PRA as stimulated by furosemide. Aprotinin at a higher dose (20,000 KIU/kg bolus and 5000 KIU/kg/min infusion for 60 minutes) significantly lowered blood pressure and increased hematocrit and PRA. These effects may be due to inhibition of serine protease(s) or to other as yet unrecognized properties of this peptide resulting from its highly cationic nature. In conclusion, aprotinin at a low dose decreased kallikrein, kinin, sodium, and water excretion. These decreases may be due to the inhibition of kallikrein and/or other serine proteases or may be secondary to the renal hemodynamic changes.(ABSTRACT TRUNCATED AT 250 WORDS)
Forebrain contributions to one-kidney renal hypertension in the rabbit.
Authors: Fink G D , Mann M E
Published: June 2012

Electrolytic lesions were placed along the anteroventral wall of the third cerebral ventricle (AV3V region) in 10 albino rabbits (AV3V-X), and sham lesions were produced in 10 additional rabbits (SHAM). Two to 3 weeks later, all rabbits underwent unilateral nephrectomy and renal artery stenosis (clip I.D. = 0.508 mm). During a 1-week control period, and for 4 weeks after renal artery stenosis, measurements were made of mean arterial pressure (MAP), heart rate, body fluid compartment volumes, plasma electrolytes, and daily sodium, potassium, and water balances. Four weeks after renal artery stenosis (RAS), cardiovascular responses to norepinephrine (NE), angiotensin II (AII), saralasin, and autonomic blockade were obtained in the conscious animals. In SHAM rabbits, MAP rose from 77 to 117 mm Hg 4 weeks after RAS. In AV3V-X rabbits, MAP rose from 77 to only 92 mm Hg 4 weeks after RAS. Body fluid compartment volumes, plasma electrolytes, and fluid, sodium, and potassium balances showed similar modest changes in both groups of rabbits. Neither saralasin infusion nor autonomic blockade caused significantly different changes in MAP between SHAM and AV3V-X rabbits 4 weeks after RAS. However, pressor responses to both NE and AII were significantly less in AV3V-X rabbits at this time. It is concluded that one-kidney, one clip renal hypertension involves activation of neurohormonal pressor mechanisms originating in the forebrain, and that the expression of these pressor mechanisms in part includes an increase in cardiovascular reactivity.
Influence of captopril treatment on angiotensin II receptors and angiotensinogen in the brain of spontaneously hypertensive rats.
Authors: Schelling P , Felix D
Published: June 2012

The brain renin-angiotensin system (RAS) has been suggested as contributing to the pathogenesis of spontaneous hypertension in rats. Brain angiotensinogen- and angiotensin II (AII)-sensitive neurons were therefore investigated in stroke-prone spontaneously hypertensive rats (SHR-sp) and in Wistar-Kyoto (WKY) rats with and without treatment by captopril (CAP). Angiotensinogen was decreased in the anterior hypothalamus but increased in the cortex, the hippocampus, and cerebellum of SHR-sp. There were no differences between SHR-sp and WKY rats concerning the angiotensinogen content of posterior hypothalamus, brain stem, and septum. The sensitivity of the septal neurons to microiontophoretically applied AII was elevated, however, in SHR-sp as compared to WKY rats with regard to threshold and maximal response for AII-evoked neuronal discharges. The excitation characteristics did not change with the age of animals in both WKY rats and SHR-sp. The treatment of SHR-sp with CAP (50 mg/kg/day per os) starting in weanlings kept animals normotensive and reduced the high sensitivity of septal neurons to AII. Simultaneously angiotensinogen content was increased in the anterior hypothalamus and suppressed in the hippocampus. The same treatment of WKY rats reduced blood pressure somewhat and increased the angiotensinogen content in the anterior hypothalamus without affecting the neuronal sensitivity to AII. Thus, malfunction of the brain RAS may participate in the hypertension of SHR-sp, since converting enzyme blockade with CAP inhibited the blood pressure rise, augmented the angiotensinogen content of the anterior hypothalamus, and decreased the sensitivity of AII receptors in the brains of these rats.
Distributions of microvascular pressure in skeletal muscle of one-kidney, one clip, two-kidney, one clip, and deoxycorticosterone-salt hypertensive rats.
Authors: Meininger G A , Harris P D , Joshua I G
Published: June 2012

Studies were performed on the cremaster skeletal muscle in rats to investigate the microvascular changes that are associated with established one-kidney, one clip (1K1C) and two-kidney, one clip (2K1C) Goldblatt hypertension and with deoxycorticosterone (DOC)-salt hypertension. Rats were anesthetized with urethane and chloralose; and cremaster muscles with intact circulation and innervation were suspended in a controlled Krebs bath. Microvascular pressures and vessel diameters were measured at three consecutive arteriolar (A) and venular (V) branch levels. Arteriolar diameters (means +/- SEM) in normotensive (NT) rats were 119 +/- 7, 86 +/- 5, and 31 +/- 3 micron respectively for 1A, 2A, and 3A arterioles; and venule diameters were 218 +/- 12, 141 +/- 15, and 53 +/- 7 micron respectively for 1V, 2V, and 3V venules. As compared to NT rats, there was a selective decrease in lumen size (percent reduction from control) for 1A and 2A (23% to 38%) in 1K1C and 2K1C rats and for 1A, 2A, and 3A (42% to 44%) in DOC rats. Venule diameters were not significantly different between normotensive and hypertensive animals at any branch level. Femoral artery pressures were significantly elevated (greater than or equal to 43%) in all three forms of hypertension; however, this increase in pressure was not proportionally transmitted throughout the microcirculation. This was evidenced by normal pressure in 3A arterioles and in all venules for 1K1C and 2K1C rats and by normal pressures in 3V and larger venules for DOC rats. Our findings indicate that elevated arterial pressure in chronic renal hypertension is not transmitted uniformly across all microvascular segments.(ABSTRACT TRUNCATED AT 250 WORDS)
Ontogeny of neural and non-neural contributions to arterial blood pressure in spontaneously hypertensive rats.
Authors: Smith P G , Poston C W , Mills E
Published: June 2012

Arterial blood pressure was measured directly by cannulation in anesthetized spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats on postnatal Days 1, 5, 9, 20, 42, and 82-86. The time course for development of the following variables was established: resting diastolic and basal (after ganglionic blockade) pressure, the neural contribution to resting pressure (resting minus basal pressure), vascular reactivity to a noradrenergic agonist, methoxamine, and to endogenous sympathetic nerve terminal norepinephrine released by tyramine (maximum pressor response and ED50) and resting and basal heart rate. Resting diastolic pressure was higher in SHR compared to WKY by 24 hours after birth. In both strains, the increase in resting diastolic pressure with age was interrupted by a plateau period (Days 5-9 in SHR; Days 9-20 in WKY). Juxtaposition of the development curves was such that the interstrain differences in pressure were statistically significant in all periods studied except Days 5 and 9. Both basal and neurally mediated components of resting diastolic blood pressure were elevated in SHR compared to WKY. The magnitude of the interstrain difference in basal pressure remained constant during development while the magnitude of the neurally mediated component showed accelerated development through 42 days of age. Reactivity to methoxamine and tyramine was higher in SHR, but the magnitude of the difference did not change with age. Cardiac sympathetic tone was higher in SHR than WKY, but did not account for the increased resting diastolic pressure in SHR.(ABSTRACT TRUNCATED AT 250 WORDS)