bluuebunny/crossref_metadata_2025 huggingface dataset:
Changes in tissue alpha- and beta-adrenergic receptors in renal hypertension in the rat.
Authors: Woodcock E A , Johnston C I
Published: June 2012

Myocardial membranes prepared from renal hypertensive rats contained reduced concentrations of both alpha- and beta-adrenergic receptors. The decrease in alpha-receptor concentration measured by [3H]-dihydroergocryptine binding was from 80 +/- 6 (SEM) to 52 +/- 2 fmol/mg. Beta-receptor concentration measured by 125I-iodohydroxybenzylpindolol binding also decreased by about half from 80 +/- 16 to 41 +/- 9 fmol/mg. The affinities of the receptors were unchanged. There was no change in either concentration or affinity of beta receptors in membranes prepared from the lungs or kidneys of these hypertensive rats. There results demonstrate that the observed receptor changes are tissue-specific. Cardiac adrenergic receptor alterations are therefore not part of a generalized adrenergic receptor decrease associated with elevated circulating plasma catecholamine concentrations, but probably reflect a specific increase in cardiac sympathetic drive.
Renomedullary deficiency in partial nephrectomy-salt hypertension.
Authors: Pitcock J A , Brown P S , Brooks B , Clapp W L , Brosius W L , Muirhead E E
Published: June 2012

Partial nephrectomy-salt hypertension (PN-SH) of the rat is associated with Na volume loading. As the hypertensive state evolves, the renomedullary interstitial cells (RIC) of the renal nubbin undergo major changes, decreasing significantly in number while the remaining ones exhibit degenerative changes. The antihypertensive action of the RIC in the renal nubbin, as measured by transplants of fragmented papillae into hypertensive recipients, virtually disappears as the hypertension develops. The changes in the RIC occur whether vascular disease of the kidney is or is not overtly present. It is suggested that deficiency of the antihypertensive action of the RIC allows the prohypertensive effects of Na volume loading to operate without proper control. Thus, the sustained hypertensive state of this model does not appear to be due solely to volume expansion. Rather, it appears due to a combination of the effects of Na and volume and a renomedullary deficiency of hormonal type. The specific cause(s) of the changes in the RIC was not determined. It seems evident that it is related to the high salt intake since the partial nephrectomy procedure without the added salt load did not alter the appearance of the RIC.
Electrolyte and hormonal effects of deoxycorticosterone acetate in young pigs.
Authors: Grekin R J , Terris J M , Bohr D F
Published: June 2012

Balances of sodium, potassium, and water were studied in the growing male pig as hypertension developed in response to subcutaneous implantation of deoxycorticosterone acetate (DOCA). Serum sodium, potassium, deoxycorticosterone (DOC), aldosterone, and plasma renin activity (PRA) were determined. These variables were observed in a total of 10 experimental and nine control pigs. All animals were uninephrectomized and fed a diet of Purina Pig Chow and tap water ad libitum. No salt was added to the food or water. Serum DOC levels rose dramatically on the day of the implantation, then gradually declined but remained approximately 10 times greater than control levels 40 days after implant. Plasma renin activity was suppressed rapidly and completely, whereas aldosterone fell only slowly to about half its control value. Sodium retention was maximum during the first 24 hours. Therefore an "escape" process became operative, causing sodium balance to return to normal after the third day, at which time the major rise in arterial pressure occurred. A marked increase in water turnover (intake and output) also began after the third day and persisted throughout the experimental period. Water balance remained normal during this period of increased turnover. Hypokalemia developed in the absence of kaliuresis, suggesting that potassium moved into the cells. Except for the potassium retention, these changes parallel the abnormalities seen in other states of mineralocorticoid excess.
Recent developments in noradrenergic neurotransmission and its relevance to the mechanism of action of certain antihypertensive agents.
Authors: Langer S Z , Cavero I , Massingham R
Published: June 2012

This report reviews a number of significant developments in the fields of noradrenergic transmission and adrenergic receptors which suggest that, in addition to the classical postsynaptic adrenoceptors, there are also presynaptic adrenoceptors that help modulate the release of norepinephrine (NE) from peripheral as well as central noradrenergic nerve endings during nerve stimulation. In particular, stimulation of presynaptic alpha-adrenoceptors reduces this release of transmitter and the reverse is observed after blockade of these receptors. Clearcut pharmacological differences exist between the postsynaptic alpha 1-adrenoceptors that mediate the responses of certain organs and the presynaptic alpha 2-adrenoceptors that modulate the NE release during nerve stimulation. Therefore, subclassification of alpha-adrenoceptors into alpha 1 and alpha 2 subtypes is warranted but must be considered to be independent of the anatomical location of these receptors. Some noradrenergic nerve endings have also been shown to possess beta-adrenergic receptors, the stimulation of which increases the quantity of transmitter released by nerve impulses. Physiologically, these receptors could be activated by circulating epinephrine (E) and be involved in essential hypertension. A third type of catecholamine receptor found at the noradrenergic nerve ending is the inhibitory dopamine (DA) receptor, which might be of significance in the development of new antihypertensive agents. Application of these new concepts of noradrenergic neurotransmission and the subclassification of alpha-adrenoceptors to the treatment of hypertension is presented. Clonidine, for example, appears to be a potent alpha 2-adrenoceptor agonist; the central receptor involved in its antihypertensive action is pharmacologically an alpha 2-type but located postsynaptically. Clonidine also induces activation of peripheral presynaptic alpha 2-adrenoceptors, which might contribute to its cardiovascular action. The antihypertensive effects of alpha-methyldopa are related to the formation of alpha-methylnorepinephrine, a preferential alpha 2-adrenoceptor agonist, which can stimulate peripheral presynaptic alpha 2-adrenoceptors leading to a decrease of NE release and a reduction in sympathetic tone. Prazosin is a new antihypertensive agent the mechanism of action of which involves a selective blockade of postsynaptic alpha 1-adrenoceptors. This drug does not antagonize several effects of clonidine that are mediated via alpha 2-adrenoceptors. The mechanisms presently considered to account for the antihypertensive activity of beta-adrenoceptor blocking agents are numerous. It is proposed that blockade of peripheral presynaptic facilitatory beta-adrenoceptors could be of significance in the antihypertensive action of these drugs.
Contribution of the sympathetic nervous system to vascular resistance in conscious young and adult spontaneously hypertensive rats.
Authors: Touw K B , Haywood J R , Shaffer R A , Brody M J
Published: June 2012

Although evidence exists for exaggerated sympathetic nervous system activity in spontaneously hypertensive rats (SHR), there are no studies in conscious animals that directly demonstrate that this increased activity is functionally involved in the elevated vascular resistance of these animals. In our present study, 8-week-old and 13-week-old SHR and Wistar Kyoto controls (WKY) were chronically instrumented with arterial and venous catheters and miniaturized pulsed Doppler flow probes on the renal and mesenteric arteries and lower abdominal aorta. While the rats were conscious and unrestrained, hexamethonium was administered intravenously to block sympathetic nervous system transmission. Prior to hexamethonium, the mean arterial pressure of young SHR and WKY averaged 123 plus or minus 5 and 109 plus or minus 4 mm Hg respectively (p smaller than 0.05), while adult SHR and WKY averaged 159 plus or minus 7 and 128 plus or minus 3 mm Hg respectively (p smaller than 0.05). Hexamethonium produced an equivalent fall in arterial pressure of young SHR (-32%) and WKY (-30%) and adult SHR (-39%) and WKY (-41%). Vascular resistance was reduced by hexamethonium in the kidney, gut, and hindquarters, but the percent changes were not significant between SHR and WKY. These data suggest that, in both young and adult SHR, vascular resistance and arterial pressure are sustained at elevated levels by some other mechanism than neurally-derived vasoconstrictor tone.
Effect of chronic hypertension and sympathetic denervation on wall/lumen ratio of cerebral vessels.
Authors: Hart M N , Heistad D D , Brody M J
Published: June 2012

The purposes of this study were to determine whether 1) cerebral vessels undergo hypertrophy during chronic hypertension and 2) sympathetic nerves contribute to cerebral vascular changes in chronic hypertension. Morphometric studies were undertaken in stroke-prone spontaneously hypertensive rats (SP-SHR) and normotensive Wistar-Kyoto (WKY) rats. Unilateral superior cervical ganglionectomy was performed in the SP-SHR at 8 weeks of age. When the rats were approximately 13 months old, they were killed and the brain was fixed with formalin at a perfusion pressure of 80% of the rat's systolic pressure. Wall/lumen ratio was measured in approximately 1200 arteries and arterioles. In parenchymal, but not pial, cerebral vessels there was pronounced vascular hypertrophy in SP-SHR: wall/lumen ratio was 0.08 in WKY and 0.14 in SP-SHR (p < 0.05). Sympathetic denervation attenuated the development of vascular hypertrophy in SP-SHR: wall/lumen ratio was 0.14 in the innervated parenchymal vessels, and 0.10 in denervated vessels (p < 0.05). We conclude that cerebral vessels undergo hypertrophy in stroke-prone SHR and speculate that vascular hypertrophy may protect cerebral vessels by reducing wall stress in chronic hypertension. Sympathetic nerves appear to exert a trophic effect on cerebral vascular muscle in chronic hypertension.
Studies on angiotensinogen of plasma and cerebrospinal fluid in normal and hypertensive human subjects.
Authors: Ito T , Eggena P , Barrett J D , Katz D , Metter J , Sambhi M P
Published: June 2012

The presence of a renin-angiotensin system in the central nervous system (CNS) has been demonstrated by several investigators, but little is known regarding the origin of its components. In this study we have compared the immunological and physical-chemical nature of angiotensinogen in plasma and cerebrospinal fluid (CSF) of human subjects and explored whether differences are present in CSF angiotensinogen concentrations of normal and hypertensive subjects. No significant differences in the nature of plasma and CSF angiotensinogen was observed with respect to molecular weight (65-70,000) electrophoretic mobility (RFalb = 0.67 plus or minus 0.003) or angiotensin I (AI) generated (pI = 6.6). Following isoelectric focusing, the plasma angiotensinogen was shown to consist of a single component with an isoionic point of 4.40 plus or minus 0.04. CSF angiotensinogen, on the other hand, resolved into three components (pI = 4.76 plus or minus 0.02; 5.16 plus or minus 0.04; 5.76 plus or minus 0.04). Although no correlations were observed between angiotensinogen levels in the CSF or plasma with blood pressure (BP), a statistically significant difference in angiotensinogen concentration of both plasma and CSF was observed between normotensive and hypertensive subjects. The differences in the chemical and immunological nature of human plasma and CSF angiotensinogens suggest that the angiotensinogen of CSF is not of peripheral origin.
Renin-secreting tumor. Case report.
Authors: Valdés G , Lopez J M , Martinez P , Rosenberg H , Barriga P , Rodriguez J A , Otipka N
Published: June 2012

Renin-secreting tumor, though rare, should be considered in assessing severe hyperreninemic, hypertensive patients. We studied an 18-year-old girl with hypokalemic hyperreninemic hyperaldosteronism. No angiographic lesion could be detected. The plasma renin activity (PRA) of the right/left renal vein was 7.3. With a presumptive diagnosis of renin-secreting tumor (RST), the patient was operated on, and a cortical nodule was found on the right lower pole. Partial nephrectomy was followed by a rapid fall in PRA (half-life, 33-44 min) and normalization of blood pressure (BP). At 3 1/2 months postoperatively, the patient showed normotension, normokalemia, normal aldosterone, and slightly elevated PRA unresponsive to postural changes and furosemide treatment. Tumoral PRA secretion responded to postural stimulus, spironolactone use, and nitroprusside-induced hypotension. Neither the high aldosterone excretion nor hyperreninemia decreased after 3 days of DOCA; this agrees with a previously reported case suggesting the usefulness of this test in the diagnosis of RST.
Blood pressure of urban Native American school children.
Authors: Gillum R F , Prineas R J , Palta M , Horibe H
Published: June 2012

In 307 Native American (NA), 1784 black (B), and 7777 white (W) children in grades 1, 2, and 3 in Minneapolis schools (99% overall response rate), blood pressure (BP) was measured supine in the right arm after 5 minutes' rest by trained technicians using a random zero BP device. In addition, height, weight, pulse rate, and triceps skinfold thickness were measured. Among children aged 6 through 9 years, NA children had slightly higher systolic BP (SBP) than B or W children overall (mean SBP: NA 106, B 104, W 105 mm Hg) and for nearly all age sex groups. In contrast, Phase 4 and 5 diastolic BP (DBP) were consistently lower in NA children ( mean DBP4: NA 64, B 69, W 67 mm Hg); NA children also had lower pulse rates, greater pulse pressures, similar or slightly lower mean BP, similar height, greater weight, body mass index, and triceps skinfold. Multiple regression analyses revealed that the slightly higher SBP in NA children was explained almost entirely by greater ponderosity. However, the lower DBP could not be explained statistically by any of the variables measured.
Renal sodium excretion and the peritubular capillary physical factors in essential hypertension.
Authors: Willassen Y , Ofstad J
Published: June 2012

Peritubular capillary hydrostatic and oncotic forces and their relationship to the renal excretion of sodium (UNaV) were examined in 19 patients with moderate and uncomplicated essential hypertension (HT) and compared with data from 20 normotensive subjects (NT). Observations were made in hydropenia (C) and during sustained isotonic saline volume expansion (E; 3% increase in body weight). The intrarenal venous pressure (IRVP) was used as an index of peritubular capillary hydrostatic pressure, and the efferent arteriolar colloid osmotic pressure (COPeff) was estimated from the arterial COP and the filtration fraction. C values (mean +/- SEM) in HT (and NT) were: arterial pressure (MAP) 110 +/- 3 mm Hg (85 +/- 1, p less than 0.001); glomerular filtration rate (GFR) 122 +/- 4 ml/min/1.73 m2 (128 +/- 3, p greater than 0.05); renal blood flow (RBF) 1172 +/- 38 ml/min/1.73 m2 (1298 +/- 48, p less than 0.05); IRVP 25.0 +/- 1.0 mm Hg (24.8 +/- 0.8, p greater than 0.05); COPeff 33.0 +/- 0.7 mm Hg (31.9 +/- 0.6, p greater than 0.05); and UNaV 140 +/- 13 mumole/min (161 +/- 12, p greater than 0.05). During E, the increase of UNaV in HT was more than double that of NT (p less than 0.001) while IRVP did not change in either group (p greater than 0.05); and COPeff fell by 26% (p less than 0.001) in both groups. GFR and RBF increased by 18% (p less than 0.001) and 19% (p less than 0.001) respectively, in HT, but did not change in NT. MAP remained unchanged in both groups. The results indicate that the peritubular capillary physical factors are normal in established essential hypertension, and that these forces are not involved in the exaggerated natriuretic response to volume expansion in essential hypertension.
Skin arteriolar responses to local temperature changes in hypertensive rats.
Authors: Unthank J L
Published: June 2012

A rat skin preparation was developed to determine if the responses of the resistance vessels to local skin warming and cooling were abnormal in spontaneously hypertensive rats (SHR). A major advantage of this preparation is that all the skin resistance vessels from small arteries preceding the microcirculation to small arterioles can be studied by intravital microscopy techniques. An abdominal skin flap was reflected with intact vasculature and positioned on a temperature-controlled manifold. Diameters of small arteries and large through small arterioles were measured at normal skin temperature (35 degrees C) and after cooling to 25 degrees C and warming to 38 degrees C, there were no differences in control diameters for comparable branching orders between normotensive (Wistar-Kyoto) and hypertensive rats; however, the maximum diameter of small arteries was 13% smaller in hypertensive rats. All arteriolar branching orders possessed vascular tone that was not altered by neural blockade with tetrodotoxin. With cooling to 25 degrees C, all branching orders constricted (range, 12-37%). The largest and smallest vessels of hypertensive rats constricted almost twice as much as their normotensive counterparts. With warming to 38 degrees C, only the smallest arterioles dilated (19% in normotensive versus 43% in hypertensive rats). This study demonstrates major differences in the arteriolar branching orders that respond to local warming and cooling of nonapical skin regions in both normotensive and hypertensive rats and also shows that skin arterioles in SHR are more responsive to local temperature changes.
Effects of OPC-21268, an orally effective vasopressin V1 receptor antagonist in humans.
Authors: Imaizumi T , Harada S , Hirooka Y , Masaki H , Momohara M , Takeshita A
Published: June 2012

An orally effective, nonpeptide vasopressin V1 receptor antagonist, OPC-21268 was produced for possible human use. We investigated the effects of OPC-21268 on the vascular effects of intra-arterially infused arginine vasopressin in human forearm vessels. The brachial artery was cannulated for drug infusions and direct measurement of arterial pressure. Forearm blood flow was measured by a strain gauge plethysmograph, and forearm vascular resistance was calculated. Arginine vasopressin was infused intra-arterially at doses of 0.02, 0.06, 0.09, 0.2, 0.6, and 1.2 ng/kg/min. The lower doses of arginine vasopressin increased, whereas the higher doses of arginine vasopressin decreased forearm vascular resistance (p less than 0.01). Intra-arterial infusion of phenylephrine at doses of 0.2, 0.4, and 2.4 micrograms/min increased forearm vascular resistance dose-dependently (p less than 0.01). OPC-21268 (50 mg for two, 100 mg for six, and 200 mg for two subjects) given orally did not alter resting arterial pressure, forearm vascular resistance, or heart rate. OPC-21268 decreased vasoconstrictor responses to arginine vasopressin at doses of 0.02 (p less than 0.02) and 0.09 (p less than 0.05) ng/kg/min and augmented vasodilator responses to arginine vasopressin at a dose of 1.2 ng/kg/min (p less than 0.01). However, the vasoconstrictor responses to phenylephrine were not altered by OPC-21268. These results demonstrated that OPC-21268 effectively and specifically antagonized the V1 receptor-mediated vasoconstriction in human forearm resistance vessels. These results suggest that OPC-21268 may be useful therapeutically to antagonize the vasoconstriction caused by arginine vasopressin in some pathological states.
Alterations in the secretion of atrial natriuretic factor in atria from aged rats.
Authors: Tummala P E , Dananberg J , Grekin R J
Published: June 2012

We measured plasma atrial natriuretic factor levels and atrial natriuretic factor secretion by isolated left atria from aging rats to determine the secretory response to stretch and adrenergic stimulation. Systolic arterial pressure and right atrial pressure were measured in vivo. Twenty-four hours later, atria were removed and studied in vitro in a perifusion system. After removal, stabilization at 0.7 g tension, and equilibration for 65 minutes, atria were stretched by increasing external tension for 20 minutes. After reequilibration atria were perifused with phenylephrine, 10(-5) M, for an additional 30 minutes. Right atrial pressure was not different between young (3 months) and aged (16-24 months) rats. Aged rats had higher plasma atrial natriuretic factor levels (52 +/- 8 versus 21 +/- 6 pmol/l; p less than 0.05) than young rats. Basal atrial natriuretic factor secretory rate in vitro was greater in atria from aged rats than young rats (875 +/- 35 versus 402 +/- 22 pg/min; p less than 0.05). Atria from aged rats had an increased response to phenylephrine compared with young rats (1,687 +/- 143 versus 788 +/- 113 pg/min; p less than 0.05) when means were adjusted for basal secretory rate. The secretory response to stretch was less than that of young rats (673 +/- 37 versus 773 +/- 27 pg/min), although this difference was not significant (p = 0.07). Atrial natriuretic factor secretion in response to adrenergic stimulation is increased with aging, and these secretory responses may contribute to increased plasma levels that occur during aging. In contrast to increased adrenergic responses, atrial natriuretic factor secretion after external stretch is not increased in aging rats.
Converting enzyme inhibition and blood pressure reactivity to psychological stressors.
Authors: Dimsdale J E , Mills P , Ziegler M , Leitz K , Nelesen R
Published: June 2012

There is considerable interest in blood pressure reactivity to psychological stressors. Because the sympathetic nervous system and the renin-angiotensin system are so responsive to stressors and are themselves the targets of many antihypertensive medications, many investigators have wondered if such medications decrease the blood pressure response to stressful stimuli. We studied 25 normotensive and 21 hypertensive men in a double-blind crossover study during which they received either placebo for 4 days or captopril (25 mg b.i.d.) for 4 days while they were hospitalized in a clinical research center. Patients were studied at resting baseline, while performing a mathematics task, and while reading out loud a disturbing newspaper article. Although captopril lowered the resting blood pressure levels, it had no effect on the amplitude of reactivity to stressors.
Job strain and ambulatory work blood pressure in healthy young men and women.
Authors: Light K C , Turner J R , Hinderliter A L
Published: June 2012

The effect of high job strain (defined as high psychological demands plus low decision latitude at work) on blood pressure was determined in 129 healthy, nonhypertensive men (n = 65) and women (n = 64). Blood pressure measures included mean screening levels obtained in a clinical environment, mean ambulatory levels from one 8-hour workday, and the change in levels from screening to mean work levels. In male workers, men with high and low job strain showed similar blood pressures at screening, but men with high job strain showed greater increases from screening to work, resulting in higher mean work blood pressure. Occupational status was unrelated to job strain or blood pressure in men. In female workers, women with high and low job strain did not differ in any measure of blood pressure; however, there were trends for higher occupational status and greater skill discretion to be associated with higher blood pressure responses at work in women.
Acute depressor effect of alcohol in patients with essential hypertension.
Authors: Kawano Y , Abe H , Kojima S , Ashida T , Yoshida K , Imanishi M , Yoshimi H , Kimura G , Kuramochi M , Omae T
Published: June 2012

To investigate the time course of the effects of alcohol on blood pressure, we studied the response of ambulatory blood pressure, neurohumoral variables, and hemodynamics to a single moderate dose of alcohol in hypertensive patients. Sixteen Japanese men (22-70 years old) with essential hypertension who were habitual drinkers were examined under standardized conditions. On the alcohol intake day, they ingested 1 ml/kg ethanol (vodka) at dinner, and on the control day they consumed a nonalcoholic beverage. The order of the two periods was randomized. Mean ambulatory blood pressure was lower in the alcohol intake period than in the control period (125 +/- 3/74 +/- 2 versus 132 +/- 4/78 +/- 2 mm Hg, p less than 0.05), and the significant depressor effect of alcohol lasted for up to 8 hours after drinking. Blood pressure on the next day did not differ with or without alcohol intake. The acute hypotensive effect of alcohol was associated with an increase in heart rate and cardiac output and with a decrease in systemic vascular resistance as determined by echocardiography. Plasma catecholamine levels and renin activity rose significantly at 2 hours after dinner, whereas vasopressin and potassium levels fell on the alcohol day. Blood glucose and serum insulin levels were comparable between the two periods. Three patients with marked alcohol-induced flush had greater hypotensive and tachycardiac responses than those who did not show an alcohol-induced flush. The change in mean blood pressure induced by alcohol was negatively correlated with age, the baseline blood pressure, and the change in plasma norepinephrine. These results indicate that the major effect of acute alcohol intake is to lower blood pressure through systemic vasodilatation in hypertensive subjects. Ambulatory blood pressure monitoring may be useful for assessing blood pressure in habitual drinkers.
Evaluation of noninvasive blood pressure monitoring devices Spacelabs 90202 and 90207 versus resting and ambulatory 24-hour intra-arterial blood pressure.
Authors: Groppelli A , Omboni S , Parati G , Mancia G
Published: June 2012

This study evaluated the accuracy of blood pressure values provided by the Spacelabs 90202 and 90207 devices in comparison with intra-arterial recording in 19 subjects at rest and in nine subjects in ambulatory conditions (Oxford method). At rest Spacelabs monitors reflected intra-arterial systolic blood pressure values very closely but overestimated to a considerable extent intra-arterial diastolic blood pressure (Spacelabs-intra-arterial differences, -0.8 +/- 9.2, NS, and 9.1 +/- 8.8 mm Hg, p less than 0.01, for systolic and diastolic blood pressures, respectively). In ambulatory conditions Spacelabs-intra-arterial average differences in 24-hour values were +0.4 +/- 5.1 mm Hg for systolic blood pressure (NS) and +14.0 +/- 2.9 mm Hg for diastolic blood pressure (p less than 0.01) when group data were considered. The performance of both Spacelabs devices was worse when assessed in individual subjects or for each hourly interval. In spite of these differences between noninvasive and intra-arterial absolute blood pressure values, however, Spacelabs 90202 and 90207 monitors were able to faithfully reflect directional hour-to-hour changes in intra-arterial blood pressure (chi 2 = 18.2 and chi 2 = 23.1 for systolic and diastolic blood pressures, respectively, p less than 0.01). No differences were found between the performance of the two Spacelabs devices. Thus, although the absolute accuracy of blood pressure values provided by these monitors in ambulatory subjects is still limited, they seem to be suitable for studies aimed at assessing 24-hour blood pressure profiles quantitatively as well as qualitatively.
Adverse effect of the calcium channel blocker nitrendipine on nephrosclerosis in rats with renovascular hypertension.
Authors: Wenzel U O , Troschau G , Schoeppe W , Helmchen U , Schwietzer G
Published: June 2012

The effect of a 6-week treatment with the calcium channel blocker nitrendipine or the angiotensin converting enzyme inhibitor enalapril on blood pressure, albuminuria, renal hemodynamics, and morphology of the nonclipped kidney was studied in rats with two-kidney, one clip renovascular hypertension. Six weeks after clipping of one renal artery, hypertensive rats (178 +/- 4 mm Hg) were randomly assigned to three groups: untreated hypertensive controls (n = 8), enalapril-treated (n = 8), or nitrendipine-treated (n = 10). Sham-operated rats served as normotensive controls (128 +/- 3 mm Hg, n = 8). After 6 weeks of treatment, renal hemodynamics (glomerular filtration rate and renal plasma flow) were measured in the anesthetized rats. Renal tissue was obtained for determination of glomerular size and sclerosis. Enalapril but not nitrendipine reduced blood pressure significantly. After 6 weeks of therapy, glomerular filtration rate was not different among the studied groups. Renal plasma flow increased, but albumin excretion and glomerulosclerosis did not change after enalapril treatment. In contrast, in the nitrendipine-treated group albuminuria increased from 12.8 +/- 2 progressively to 163 +/- 55 compared with 19.2 +/- 9 mg/24 hr in the hypertensive controls. Furthermore, glomerulosclerosis index was significantly increased in the nitrendipine-treated group compared with the hypertensive controls (0.38 +/- 0.1 versus 0.13 +/- 0.04). In addition, glomerular size was higher in the nitrendipine-treated group (14.9 +/- 0.17 10(-3) mm2) but lower in the enalapril-treated group (11.5 +/- 0.15 10(-3) mm2) compared with the hypertensive controls (12.1 +/- 0.17 10(-3) mm2).(ABSTRACT TRUNCATED AT 250 WORDS)
Hematocrit, blood pressure, and hypertension. The Gubbio Population Study.
Authors: Cirillo M , Laurenzi M , Trevisan M , Stamler J
Published: June 2012

Baseline data from the Gubbio Population Study in north central Italy were used to investigate the relation of hematocrit to blood pressure and hypertension among 2,809 men and women aged 25-74 years. Independent of gender, age, and other confounders, the hypertensive group had a higher hematocrit than the nonhypertensive group (p less than 0.001). In comparison with the untreated hypertensive group, the hypertensive group being treated with diuretics or with other drugs only had similar mean hematocrit levels despite significantly lower blood pressures. Hematocrit was positively correlated with systolic pressure (r = 0.085, p less than 0.01 and r = 0.264, p less than 0.001 for men and women, respectively) and diastolic pressure (r = 0.214, p less than 0.001 and r = 0.266, p less than 0.001). In both sexes, whether or not the treated hypertensive group was included, age-adjusted prevalence of hypertension and average blood pressure were higher for persons in higher quintiles of hematocrit (p less than 0.001). The association of hematocrit with blood pressure and hypertension was significant and independent of several confounders. The regression coefficient of blood pressure on hematocrit ranged between 0.410 and 0.620 mm Hg per unit of hematocrit for systolic pressure and between 0.371 and 0.581 for diastolic pressure, depending on gender and whether the treated hypertensive group was included in multiple regression analysis. Based on exponentiation of the multiple logistic coefficient, prevalence of hypertension was at least two times greater for persons whose hematocrit levels were higher by 10 units.
Neurotransmission through sympathetic ganglia of spontaneously hypertensive rats.
Authors: Magee J C , Schofield G G
Published: June 2012

Transmission of neuronal activity was assessed by recording preganglionic and postganglionic compound action potentials in superior cervical ganglia isolated from adult spontaneously hypertensive rats (SHR), Wistar-Kyoto (WKY) rats, and Wistar rats as well as young SHR and WKY rats to determine if previously observed alterations of membrane excitability, synaptic transmission, or both, have an effect on the transmission of preganglionic activity in SHR. Single stimuli induced more postganglionic neurons to fire over a wide range of preganglionic stimulation intensities in superior cervical ganglia from adult SHR as compared with those from adult normotensive controls. Short stimulation trains confirmed that SHR are able to maintain this greater number of active postganglionic neurons during low-frequency stimulation (1-20 Hz). However, by the end of a train of high-frequency stimulation (70-100 Hz) fewer neurons fired in ganglia from SHR compared with those from normotensive controls. These differences in transmission were not observed in the young rats. The results from the present study demonstrate that physiological frequencies of preganglionic activity are more effectively transmitted through sympathetic ganglia from adult SHR compared with those from normotensive controls, and this enhanced transmission through ganglia may contribute to the elevated sympathetic activity and the consequent hypertension seen in this model.
Atrial natriuretic peptide modulates baroreceptor reflex in spontaneously hypertensive rat.
Authors: Jin H , Yang R H , Calhoun D A , Wyss J M , Oparil S
Published: June 2012

Our previous studies have suggested that atrial natriuretic peptide in the caudal nucleus tractus solitarii is involved in the centrally mediated regulation of blood pressure in the salt-sensitive spontaneously hypertensive rat (SHR). The current study tested the hypothesis that endogenous atrial natriuretic peptide in the caudal nucleus tractus solitarii participates in baroreceptor reflex control of heart rate in this hypertensive model. Salt-sensitive SHR and control Wistar-Kyoto (WKY) rats maintained on basal (1%) salt intake were studied. Arterial baroreceptor reflex-mediated changes in heart rate were recorded in conscious unrestrained rats during phenylephrine (5-40 micrograms.kg-1.min-1 infusion; 30 minutes later, atrial natriuretic peptide (50 ng), monoclonal antibody to atrial natriuretic peptide (0.55 micrograms), purified mouse immunoglobulin G (0.55 micrograms), or artificial cerebrospinal fluid vehicle (50 nl) was microinjected into the caudal nucleus tractus solitarii. Phenylephrine infusion was then repeated and mean arterial pressure and heart rate were monitored as before. The slope of the heart rate/mean arterial pressure relation was significantly less (p less than 0.05) in the salt-sensitive SHR than in the WKY control, indicating that baroreceptor reflex control of heart rate was blunted in this hypertensive model. Microinjection of atrial natriuretic peptide into the caudal nucleus tractus solitarii further blunted (p less than 0.05) baroreceptor reflex control of heart rate in salt-sensitive SHR but not in WKY rats. In contrast, microinjection of the monoclonal antibody enhanced the sensitivity of baroreceptor reflex control of heart rate in salt-sensitive SHR but not in WKY rats.(ABSTRACT TRUNCATED AT 250 WORDS)
Increased platelet angiotensin II receptor number in pregnancy-induced hypertension.
Authors: Graves S W , Moore T J , Seely E W
Published: June 2012

Women with pregnancy-induced hypertension (PIH) are characterized by relatively greater blood pressure sensitivity to exogenous angiotensin II (Ang II) than normotensive pregnant women. Evidence suggests that this is due to an alteration in Ang II receptor sites. However, the question of whether this represents an increase in receptor number or affinity remains unanswered. To answer this question Ang II receptors on platelets from normotensive women during each trimester of pregnancy and the postpartum period were studied and compared with platelet Ang II binding in third trimester women with PIH and in postpartum women who had had a recent pregnancy complicated by PIH. We also measured plasma renin activity, Ang II, and aldosterone in blood samples from these women and sodium and creatinine in 24-hour urine collections. Normotensive pregnant women had significantly less platelet Ang II binding than nonpregnant, postpartum women (0.85 +/- 0.19 versus 2.87 +/- 0.83%, p = 0.003), reflecting a reduction in receptor number but not affinity. This probably reflects the significant increase in Ang II during pregnancy. Urinary sodium excretion was equivalent and could not explain these changes. Comparisons of third trimester women with PIH against those without PIH documented a significantly higher Ang II binding in the women with PIH (2.23 +/- 0.42 versus 0.85 +/- 0.19%) that was caused by an increase in receptor number (6.0 +/- 1.3 versus 3.0 +/- 0.8 fmol Ang II per 5.6 x 10(8) platelets, p = 0.047) but similar Ang II binding affinity. This reflected significantly lower Ang II levels.(ABSTRACT TRUNCATED AT 250 WORDS)
Lovastatin but not enalapril reduces glomerular injury in Dahl salt-sensitive rats.
Authors: O'Donnell M P , Kasiske B L , Katz S A , Schmitz P G , Keane W F
Published: June 2012

Dahl salt-sensitive (S) rats fed a high salt diet develop hypertension, hyperlipidemia, and progressive renal disease. Previous studies have suggested that lipids may be important in the pathogenesis of glomerulosclerosis in Dahl S rats. To investigate this possibility, Dahl S rats fed 4% NaCl chow were treated chronically with the cholesterol synthesis inhibitor lovastatin. After 22 weeks, lovastatin-treated rats had a 38% reduction in serum cholesterol, a 76% reduction in urine albumin excretion, and one-sixth the incidence of focal glomerulosclerosis compared with vehicle-treated control rats. Blood pressure in lovastatin-treated rats was significantly (p < 0.05) lower than that in vehicle-treated rats both early in the study (4 weeks of treatment) and at the end of the protocol. Lovastatin had no effect on glomerular filtration rate or glomerular ultrafiltration dynamics. The efficacy of angiotensin converting enzyme inhibitors in attenuating proteinuria and experimental glomerular disease may be dependent on sodium intake. Thus, we also investigated the effects of long-term enalapril treatment on glomerular injury in Dahl S rats fed high salt chow. Enalapril treatment (50 or 200 mg/l drinking water) significantly lowered blood pressure in Dahl S rats, but did not significantly affect albuminuria or glomerulosclerosis. Enalapril also had no effect on glomerular hemodynamics. These results suggest that lipids may be important in the development of both glomerular disease and hypertension in Dahl S rats and that angiotensin converting enzyme inhibition may not affect the course of renal disease in a setting of high salt intake.
Whole body autoregulation in reduced renal mass hypertension.
Authors: Hinojosa-Laborde C , Frohlich B H , Cowley A W
Published: June 2012

Whole body autoregulation in conscious rats can be shown in the absence of the rapid acting neural and hormonal controllers of blood pressure. It is hypothesized that this phenomenon is responsible for the gradual rise of vascular resistance observed in volume-dependent forms of hypertension such as reduced renal mass-salt-induced hypertension. To examine the hypothesis, we evaluated the gain of whole body autoregulation at various stages of reduced renal mass hypertension to determine if acute autoregulatory capacity is altered during chronic hypertension. Rats underwent reduced renal mass surgery (nephrectomy plus 70% reduction of remaining kidney) and were studied at 2 (n = 8), 4 (n = 6), and 6 (n = 7) weeks after high salt diet. Control rats (n = 6) underwent nephrectomy and sham surgery and were studied after 2 weeks of high salt diet. All reduced renal mass rats showed progressive hypertension (2 weeks, 136 +/- 5; 4 weeks, 157 +/- 8; and 6 weeks, 171 +/- 10 mm Hg) compared with sham rats (113 +/- 4 mm Hg). We observed an increase in basal level of total peripheral resistance index after neurohumoral blockade in reduced renal mass rats (2 weeks, 1.64 +/- 0.06; 4 weeks, 1.79 +/- 0.10; and 6 weeks, 1.89 +/- 0.09 mm Hg.100 g-1.min-1.ml-1) compared with sham rats (1.56 +/- 0.10 mm Hg.100 g-1.min-1.ml-1).(ABSTRACT TRUNCATED AT 250 WORDS)
Fasting insulin in relation to subsequent blood pressure changes and hypertension in women.
Authors: Lissner L , Bengtsson C , Lapidus L , Kristjansson K , Wedel H
Published: June 2012

The role of hyperinsulinemia in the development of hypertension is not well understood, particularly insofar as both conditions relate to obesity. The present analysis examines the hypothesis that hyperinsulinemia, independent of obesity, precedes hypertension and natural blood pressure increases in women. The subjects were 50-year-old women from a prospective population study in Gothenburg, Sweden. Fasting insulin levels were determined at baseline (1968-1969) and were evaluated in relation to subsequent hypertension. Blood pressures were measured at the initial physical examination and at the 6- and 12-year follow-up examinations. The first analysis presented here (n = 278) identified incident cases of hypertension during the 12-year follow-up period, whereas the second analysis (n = 219) examined continuous changes in blood pressure. In both analyses, degree, type, and changes in obesity were considered as possible confounding factors. High fasting insulin values were predictive of subsequent incidence of hypertension over the 12-year follow-up period. Subjects with insulin values above the 75th percentile experienced three times more hypertension than did those below the 25th percentile. There was also a significant association between insulin at baseline and increases in diastolic (but not systolic) blood pressure. The positive relations between fasting insulin, on one hand, and diastolic blood pressure changes and hypertension, on the other, could not be explained by confounding effects of body mass index, waist/hip ratio, or weight gain. These findings are consistent with the hypothesis that fasting insulin levels may be one predisposing factor in the etiology of hypertension.
Silent cerebral infarction as a form of hypertensive target organ damage in the brain.
Authors: Hougaku H , Matsumoto M , Kitagawa K , Harada K , Oku N , Itoh T , Maeda H , Handa N , Kamada T
Published: June 2012

The incidence, number, size, and location of silent cerebral infarction on 0.1 T magnetic resonance imaging was investigated in 66 hypertensive patients (63 +/- 9 years old; mean +/- SD) and 42 age-matched normotensive subjects (61 +/- 9 years old) to determine the clinical significance of hypertension in silent cerebral infarction. Cerebrovascular risk factors and the severity of hypertensive changes in other major target organs were also investigated. The incidence of silent infarction in hypertensive patients (47%) tended to be higher than that of normotensive subjects (33%) and increased significantly with advancing age. In hypertensive patients, a significantly higher incidence of silent lesions was noted in patients with hypertensive changes in major target organs (72-73% in patients with organ involvement versus 33-39% in those without). The average number of lesions in hypertensive patients was significantly higher than that in normotensive subjects (6.0 versus 2.1), and the lesions in the hypertensive patients were more frequently detected in the brain areas supplied by perforating arteries than those in normotensive subjects (47% versus 24%). These results clearly demonstrate that silent cerebral infarction is frequently seen in older hypertensive patients, especially when moderate hypertensive changes are noted in major target organs, and suggest that hypertensive arterial changes play a crucial role in the occurrence of silent infarction.
Morphology of renal afferent arterioles in spontaneously hypertensive rats.
Authors: Skov K , Mulvany M J , Korsgaard N
Published: June 2012

We present a new perfusion technique that allows arteries down to the level of capillaries to be fixed while relaxed and under a known intravascular pressure. Through a catheter inserted into the right renal artery of 12-week-old male spontaneously hypertensive rats (n = 9) and control Wistar-Kyoto rats (n = 11), the kidney vessels were rinsed with human plasma, relaxed by papaverine, and perfused with a casting resin containing microspheres. The microspheres (12 microns) became trapped in the glomeruli of the kidney and, together with a closing of the venous outflow, they caused the flow through the kidney to stop, so that the intravascular pressure was raised to the level of the input perfusion pressure (100 mm Hg). The resin material was allowed to harden, and the kidney was immersion-fixed and prepared for histomorphometrical investigations. This technique made it possible to measure both the structurally determined lumen diameter and the corresponding media thickness under clearly defined conditions. The lumen diameter of afferent arterioles close to the glomeruli showed a 17% reduction in spontaneously hypertensive rats (15.4 +/- 0.6 microns; mean +/- SEM) compared with Wistar-Kyoto rat arterioles (18.5 +/- 0.3 microns, p < 0.001). However, this was not due to media hypertrophy, because media cross-sectional area was smaller (p < 0.001) in spontaneously hypertensive rats (210 +/- 6 microns 2) compared with Wistar-Kyoto rats (274 +/- 16 microns 2). We conclude that the lumen reduction in renal afferent arterioles in spontaneously hypertensive rats is not the result of an encroachment on the lumen by a hypertrophic media.
Development of hypertension in animals with reduced total peripheral resistance.
Authors: Huang M , Hester R L , Coleman T G , Smith M J , Guyton A C
Published: June 2012

The object of the present study was to determine whether deoxycorticosterone acetate (DOCA)-salt hypertension can be produced in rats in the presence of low total peripheral resistance (TPR) induced by long-term administration of minoxidil, a vasodilator. The rats were divided into four groups: sham-control, DOCA-salt, minoxidil, and DOCA-salt with minoxidil. The rats in both DOCA groups had DOCA pellets implanted subcutaneously and were given saline to drink. The rats in both minoxidil groups were given minoxidil (3 mg/day) in the drinking water throughout the experiment. Final measurements, including mean arterial blood pressure, cardiac index, and renal blood flow were made after 4-6 weeks. Flow measurements were made using radioactive microspheres. Cardiac index (ml.min-1.100 g-1) in sham-control rats averaged 18 +/- 2 and was higher in the other groups: 23 +/- 4 (DOCA-salt), 25 +/- 2 (minoxidil), and 30 +/- 2 (DOCA-salt plus minoxidil). Mean arterial pressure (mm Hg) was increased in both DOCA-salt rats (160 +/- 8) and DOCA-salt plus minoxidil rats (153 +/- 5) as compared with sham-control (116 +/- 2) and minoxidil (113 +/- 3) rats. There was no significant difference in TPR between the sham-control and DOCA-salt rats, but TPR in minoxidil and DOCA-salt plus minoxidil rats was 30% and 28% lower than that in untreated sham-control and DOCA-salt hypertensive rats, respectively. In contrast, renal vascular resistance was significantly increased in both DOCA-salt groups as compared with non-DOCA-salt groups.(ABSTRACT TRUNCATED AT 250 WORDS)
Twenty-four-hour blood pressure profiles in normotensive sons of hypertensive parents.
Authors: Schwartz G L , Turner S T , Sing C F
Published: June 2012

We investigated whether blood pressures are higher in normotensive offspring of hypertensive parents than in normotensive offspring of normotensive parents outside the physician's office and, if so, whether these higher blood pressures are dependent on the level of dietary sodium intake. We compared 24-hour ambulatory blood pressure profiles between 11 normotensive sons of two hypertensive parents and 11 normotensive sons of two normotensive parents; profiles were recorded after 1 week of a low sodium diet (10 meq/day) and after 1 week of a high sodium diet (200 meq/day). The sons of hypertensive parents were on average 6 years older than the sons of normotensive parents (47 +/- 5 [SD] versus 41 +/- 4 years, p < 0.05). The shift from low to high sodium diet did not significantly change the magnitude of differences in office or ambulatory blood pressures between the groups (i.e., no group-by-diet interaction); thus, we assessed group effects by contrasting blood pressure means for each group pooled across diets. Age-adjusted office blood pressure was higher in sons of hypertensive parents than in sons of normotensive parents (116 +/- 7/80 +/- 6 versus 111 +/- 7/75 +/- 6 mm Hg; p = 0.020 for systolic and p = 0.003 for diastolic blood pressure).(ABSTRACT TRUNCATED AT 250 WORDS)