bluuebunny/crossref_metadata_2025 huggingface dataset:
Removal of endothelium-dependent relaxation by antibody and complement in afferent arterioles.
Authors: Juncos L A , Ito S , Carretero O A , Garvin J L
Published: August 2012

Studies of endothelial regulation of microvascular function have been hampered by the technical difficulty of removing the endothelium without damaging the vascular smooth muscle cells. This study presents a novel method of endothelial damage and lysis based on the facts that endothelial cells express specific antigens and that complement reacts with antibody/antigen complexes, causing cell lysis. We isolated and perfused rabbit glomerular afferent arterioles in vitro and examined vascular responses before and after treating them with an antibody against factor VIII-related antigen and complement. The treatment consisted of perfusing afferent arterioles with medium containing the antibody and complement for 10 minutes, followed by a 20-minute washout period. Before treatment, acetylcholine and the calcium ionophore A23187 (receptor- and nonreceptor-mediated endothelium-dependent vasodilators, respectively) dilated norepinephrine-preconstricted afferent arterioles, whereas neither dilated the arterioles after treatment, suggesting loss of endothelium-dependent vasodilation. In contrast, responses to nicardipine and norepinephrine (endothelium-independent vasodilator and constrictor, respectively) were not altered by the treatment, indicating intact vascular smooth muscle cell function. Transmission electron microscopy revealed that the antibody- and complement-treated arterioles had various degrees of endothelial damage, including areas of detachment from the basement membrane and marked loss of the number and structure of mitochondria, but no evidence of vascular smooth muscle cell damage. These results indicate that treatment with anti-factor VIII-related antigen antibody and complement is an effective method for eliminating endothelium-dependent vasodilation without altering endothelium-independent responses. Thus, this method may be useful for studying the functional role of the endothelium in microvessels.
Blockers of the L-arginine-nitric oxide-cyclic GMP pathway facilitate baroreceptor resetting.
Authors: da Silva S V , da Silva V J , Ballejo G , Salgado M C , Salgado H C
Published: August 2012

We investigated the role of nitric oxide on rapid (25- and 40-minute) baroreceptor resetting during the onset of acute hypertension in rats treated with NG-nitro-L-arginine, an inhibitor of nitric oxide synthesis, and methylene blue, an inhibitor of guanylate cyclase. The effect of treatment with glibenclamide, an ATP-dependent K+ channel blocker, was also investigated. Arterial hypertension was provoked in a ramp progression by the drug NG-nitro-L-arginine alone or in association with aortic coarctation. Whole aortic nerve activity and carotid pressure were recorded in the anesthetized rats. The extent of rapid resetting was evaluated by means of the ratio (delta Systolic Threshold Pressure/delta Control Diastolic Pressure) x 100 as well as by the extent of displacement of the pressure-nerve activity curve defined by the ratio (delta Mean Arterial Pressure at 50% of maximum activity/delta Mean Arterial Pressure) x 100. All groups gave the same increase in mean arterial pressure at 25 and 40 minutes after the onset of hypertension. A greater extent of resetting to hypertensive levels was observed in the treated groups compared with coarctation alone. At 40 minutes after the onset of hypertension, the coarctation and nitro-L-arginine groups exhibited a further increase in the extent of resetting. The rats submitted to glibenclamide plus coarctation presented a slight but significant decrease in gain. These findings suggest that an active L-arginine-nitric oxide-cyclic GMP pathway blunts rapid resetting during the onset of hypertension. In addition, they also indicate that ATP-dependent K+ channels can also modulate rapid resetting of the baroreceptors to hypertensive levels.
DuP 753 is more effective than captopril on baroreceptor function in high-renin hypertension.
Authors: Moreira E D , Ida F , Pires M D , Krieger E M
Published: August 2012

High-renin hypertensive rats exhibit a general impairment of the baroreceptor reflexes. In the present study we compared the effect of the angiotensin converting enzyme inhibitor captopril (10 mg/kg per day) with the effect of the selective angiotensin subtype 1 receptor blocker DuP 753 (10 mg/kg per day) on the baroreceptor reflex bradycardia (progressive doses of phenylephrine) and baroreceptor reflex tachycardia (progressive doses of nitroprusside) in conscious rats 7 days after aortic ligation. Arterial pressure was markedly reduced after both acute (15-minute) treatment with captopril (123 +/- 6 versus 184 +/- 23 mm Hg) and DuP 753 (140 +/- 10.5 versus 181 +/- 5.4 mm Hg), but the depressed baroreceptor reflex bradycardia increased only after DuP 753 (1.13 +/- 0.22 versus 0.75 +/- 0.60 beats per minute [bpm]/mm Hg) and remained attenuated after captopril (0.54 +/- 0.086 versus 0.30 +/- 0.07 bpm/mm Hg). After a 2-day treatment, captopril reduced arterial pressure (95 +/- 5 versus 184 +/- 2.3 mm Hg) to lower levels than DuP 753 (119 +/- 6 versus 172 +/- 4.6 mm Hg), whereas the depressed baroreceptor reflex bradycardia remained unchanged with captopril (0.46 +/- 0.13 versus 0.31 +/- 0.076 bpm/mm Hg) and increased with DuP 753 (1.13 +/- 0.19 versus 0.38 +/- 0.12 bpm/mm Hg). Neither DuP 753 nor captopril administered acutely (15 minutes) or for 2 days significantly altered the depressed baroreceptor reflex tachycardia.(ABSTRACT TRUNCATED AT 250 WORDS)
Hemodynamic effects elicited by stimulation of the nucleus tractus solitarii.
Authors: Yin M , Lee C C , Ohta H , Talman W T
Published: August 2012

Microinjection of the excitatory amino acid L-glutamate into the nucleus tractus solitarii (NTS) elicits decreases in arterial pressure and heart rate. In the present study, we sought to determine the regional hemodynamic effects that were correlated with changes in arterial pressure and heart rate produced by stimulation of the NTS. In anesthetized rats, blood flow in the renal (RBF), superior mesenteric (MBF), and hindquarter (HBF) vascular beds was measured by pulsed Doppler flowmeters. Relative vascular resistances (RVR, MVR, and HVR) were calculated by dividing mean arterial pressure (mm Hg) by the Doppler shift (kHz). Microinjection of L-glutamate into the NTS caused rapid, transient, dose-related decreases in mean arterial pressure and heart rate. MVR and RVR were minimally changed immediately after injections, but both demonstrated delayed dilatation. In contrast, HVR fell immediately but demonstrated delayed constriction. Identical changes occurred in intact rats and in those with interruption of the baroreflex by sinoaortic denervation. Ganglionic blockade with hexamethonium abolished virtually all L-glutamate-induced responses. This study suggests that NTS neurons exert differential effects on renal, mesenteric, and hindquarter vascular beds and that glutamate-induced regional hemodynamic changes are mediated predominantly through autonomic pathways.
Effects of age and hypertension on autonomic nervous regulation during passive head-up tilt.
Authors: Yo Y , Nagano M , Nagano N , Iiyama K , Higaki J , Mikami H , Ogihara T
Published: August 2012

To study the effects of age and hypertension on autonomic nervous function with passive postural change, we examined 31 normotensive subjects (25 to 85 years old) and 31 hypertensive patients (21 to 71 years old) without any cardiac disease, diabetes mellitus, or neurological disorders. Subjects were passively placed in a 60 degrees head-up tilting position after 15 minutes in the supine position. Autonomic nervous function was evaluated by frequency domain analysis of heart rate with the autoregressive method. Using low-frequency (0.1 Hz) and high-frequency (0.25 Hz) peaks, the ratio of low- to high-frequency power (L/H) was calculated as an index of sympathetic activity and the ratio of high to total power (%HF) as that of parasympathetic activity. With the patient in the supine position, total power spectral density declined logarithmically with age in normotensive subjects and hypertensive patients, but %HF and L/H showed no changes. In response to passive tilting, L/H was increased and %HF was decreased in the normotensive subjects, and these responses declined with age logarithmically. In contrast, hypertensive patients exhibited less autonomic response to postural change regardless of age. These results suggest that autonomic neural response to tilt is decreased with age; however, attenuation of the response by hypertension is not associated with an increase in age.
Alteration of response to neuropeptide Y in the nucleus tractus solitarius of spontaneously hypertensive rats.
Authors: Takesako T , Takeda K , Kuwahara T , Takenaka K , Tanaka M , Itoh H , Nakata T , Sasaki S , Nakagawa M
Published: August 2012

In normotensive rats, microinjections of neuropeptide Y (2.5 to 25 pmol) into the unilateral nucleus tractus solitarius elicited dose-dependent vasodepressor and bradycardiac responses accompanied by an inhibition of sympathetic nerve firing. After microinjections of the alpha 2-adrenergic receptor antagonist yohimbine (100 ng) into the nucleus tractus solitarius, the depressor and bradycardic responses to the injection of neuropeptide Y (25 pmol) into the nucleus tractus solitarius were significantly attenuated. In contrast, pretreatment with the alpha 1-adrenergic receptor antagonist doxazosin (200 ng) injected into the nucleus tractus solitarius did not alter these responses. In spontaneously hypertensive rats, microinjections of neuropeptide Y (25 pmol) into the nucleus tractus solitarius also elicited depressor and bradycardic responses that were significantly less than those of normotensive Wistar-Kyoto rats. However, pretreatment with yohimbine (100 ng) in the nucleus tractus solitarius did not diminish these depressor responses in spontaneously hypertensive rats. Depressor responses to neuropeptide Y, which was administered after yohimbine pretreatment, were also less in Wistar-Kyoto rats than in spontaneously hypertensive rats. The results suggest that the depressor and bradycardic responses elicited by neuropeptide Y were accompanied by the inhibition of sympathetic nerve activity. These responses may be mediated in part by alpha 2-adrenergic receptor in the nucleus tractus solitarius. The impairment of alpha 2-adrenergic receptor-mediated responses to neuropeptide Y in spontaneously hypertensive rats may contribute to the development of hypertension.
Vasopressin-central nervous system interactions in the development of DOCA hypertension.
Authors: Berecek K H , Barron K W , Webb R L , Brody M J
Published: August 2012

DOCA-salt hypertension does not develop in rats with hereditary lack of vasopressin (DI rats) nor in rats with lesion of the anteroventral region of the third ventricle (AV3V), an area controlling vasopressin (VP) release. We examined, therefore, the effect of VP treatment on the development of DOCA salt hypertension in AV3V-lesioned (AV3V-L) normal Sprague-Dawley rats and in Brattleboro rats homozygous for diabetes insipidus (DI rats). We also examined changes in vascular reactivity in isolated, perfused kidneys in the experimental groups. Whereas sham-lesioned (SL) rats showed hypertension at 5 weeks, AV3V-L rats showed no change in arterial pressure (AP) after DOCA. AV3V-L rats given VP exhibited only an intermediate rise in AP in spite of the fact that plasma VP levels were comparable in DOCA-treated SL rats and AV3V-L rats. SL and AV3V-L rats given VP showed enhanced renal vascular activity whereas no vascular changes occurred in AV3V-L rats. At 5 weeks post DOCA, intact DI rats given VP were hypertensive and exhibited enhanced renal vascular reactivity. AV3V lesion in DI rats completely prevented VP-induced DOCA/salt hypertension and enhanced vascular responsiveness. These data suggest that VP plays a primary role in DOCA-salt hypertension through an induction of enhanced vascular reactivity and through central mechanisms requiring the integrity of the AV3V region.
Alterations in osmotic but not pressor responses to ACTH by optic recess lesions in sheep.
Authors: Scoggins B A , Coghlan J P , Congiu M , Denton D A , Graham W F , McKinley M J , Mason R T , Smith M H , Tresham J , Weisinger R S , Wright R D
Published: August 2012

This study examines whether neural structures in the region of the optic recess of the third ventricle may be involved in the genesis of adrenocorticotrophic hormone (ACTH)-induced hypertension in sheep. Five sheep were prepared with lesions in an area of the forebrain that included the organum vasculosum of the lamina terminalis (OVLT) and surrounding periventricular tissue. In these animals the dipsogenic response to systemically infused hypertonic sodium chloride (NaCl) was abolished. ACTH treatment (20 micrograms/kg/day) for 5 days caused an increase in mean arterial pressure (MAP) of 19 mm Hg, a response identical to that seen in normal sheep. With ACTH treatment, increases in plasma osmolality were greater than normal, but polydipsia did not occur in the lesioned sheep. In six other sheep with lesions either lateral or anterior to the optic recess of the third ventricle, the dipsogenic response to hypertonic NaCl and pressor response to ACTH were normal. These studies establish that in ACTH-treated sheep the integrity of the anterior ventral part of the third ventricle is not essential for the development of the hypertension. This is in contrast to the finding in other models of experimental hypertension in the rat.
Altered neural control of cardiovascular function in sodium-depleted dogs.
Authors: Takishita S , Ferrario C M
Published: August 2012

Sodium restriction affects sympathetic control mechanisms by blunting of the reflex pressor response to carotid sinus hypotension, which is reversible by section of vagal afferents. To obtain more direct evidence, sympathetic nerve activity was recorded from a renal nerve (RNA) in 16 normal (NS) and 13 sodium-depleted (SD) dogs anesthetized with morphine-pentobarbital. Integrated RNA was measured during changes in mean arterial pressure (MAP) produced by i.v. infusion of sodium nitroprusside (100 micrograms/kg/min) or phenylephrine (20 micrograms/kg/min). The classical inverse relationship between MAP and integrated RNA was found before and after bilateral vagotomy (VAGT) in both NS and SD dogs. However, RNA in SD dogs, expressed as % of maximal neural firing, was significantly less at any blood pressure level when compared to NS dogs. In addition, the critical pressure (point at which RNA ceased) was reduced in SD vs NS dogs (p less than 0.002). The decreased sympathetic neural firing in SD dogs was abolished after bilateral VAGT, confirming the pronounced buffering effects of vagal afferents on RNA in salt-depleted dogs.
Antibodies to the alpha 1- and alpha 2-selective antagonists prazosin and yohimbine as probes of the alpha-adrenergic binding sites.
Authors: Graham R M , Hess H J , Haber E , Homcy C J
Published: August 2012

Antibodies were raised against a newly synthesized analog (CP57,609) of the alpha 1-selective antagonist prazosin, and against the alpha 2-selective antagonist, yohimbine, by immunization of rabbits with antigens prepared by covalent linkage of these ligands to albumin. Competitive inhibition of [3H]prazosin binding to anti-CP57,609 antiserum by a variety of unlabeled ligands revealed a spectrum of antibody specificity, with alpha 1-selective agents competing more potently than alpha 2-selective ligands. In contrast, alpha 2-selective ligands competed more potently with the binding of [3H]yohimbine to the anti-yohimbine antiserum than alpha 1-selective agents. These respective antisera were subjected to affinity fractionation of a CP57,609- or yohimbine-Sepharose 4B resin. Fractions from the CP57,609 resin were eluted successively with phentolamine (10(-3)M), prazosin (10(-4)M), and guanidine (5M), and from the yohimbine resin with prazosin (10(-4)M), yohimbine (10(-4)M), and guanidine (5M). The binding profiles of these fractions differed, and in certain fractions the relative order of potency of adrenergic agents was almost identical to that observed with membrane alpha-adrenergic receptors. Moreover, using these eluted fractions as immunogens, antisera have been obtained which, in the initial bleeds, already possess antiidiotypic activity. These findings therefore suggest that affinity fractionation of antibodies raised against alpha 1- and alpha 2-selective antagonists may provide useful analogs for the further study of the ligand recognition properties of alpha-adrenergic receptors. Additionally, it is probable that antiidiotypic antisera will be developed which will recognize the alpha-adrenergic binding sites.
Effect of pheochromocytoma and hypophysectomy on blood pressure and catecholamines in NEDH rats.
Authors: Manger W M , Hulse M C , Forsyth M S , Chute R N , Brown C E , Webb K , Sussman R , Warren S
Published: August 2012

The New England Deaconess Hospital (NEDH) rat provides a valuable model with which to study pheochromocytoma (P); 59% of male rats 700 to 900 days old and 81% of those 900 days or older developed spontaneous P. One transplantable P (P259), when implanted into other NEDH rats, markedly increased plasma norepinephrine and dopamine as well as blood pressure, and usually caused death within 4 weeks. Even without P, about 83% of NEDH rats became hypertensive by 131/2 weeks of age and remained moderately hypertensive until 2 years of age when some animals developed spontaneous P and hypertension became severe. Whether a common mechanism is responsible for early appearance of hypertension and later development of P remains to be determined. Hypophysectomized NEDH rats remained normotensive or slightly hypotensive despite marked elevations of plasma norepinephrine and dopamine caused by P259 implantation; furthermore, survival was prolonged to 3 months. Catecholamine concentrations in plasma and RBC were usually quite similar, indicating that red blood cells play a significant role in inactivating circulating catecholamines. Unlike the normal adrenal, P259 in NEDH rats contains mainly norepinephrine and dopamine with little epinephrine; it appears that P259 is deficient in the enzyme phenylethanolamine-N-methyltransferase (PNMT), which converts norepinephrine to epinephrine. Why hypophysectomy prevents hypertension and prolongs life in rats with P259 implants is unclear; adrenal cortical and thyroid deficiency may play a role. Preliminary observations indicate that hypophysectomy can prevent spontaneous development of P in NEDH rats.
Relationship of vascular sodium-potassium pump activity to intracellular sodium in hypertensive rats.
Authors: Brock T A , Smith J B , Overbeck H W
Published: August 2012

The activity of the sodium-potassium (Na+-K+) pump in arterial tissue from rats with chronic DOCA-salt or one-kidney Grollman renal hypertension was assayed in vitro as the rate of ouabain-sensitive 86Rb+ uptake. Estimates of total cell Na+ and tissue K+ were made by a lithium-substitution method on the same segment of arterial tissue. In both freshly excised tail arteries and aortas, and in aortas after overnight cold storage at 4 degrees C and a 3-hour equilibration at 37 degrees in Krebs-Henseleit, cell Na+ content did not differ significantly between control and hypertensive groups. However, ouabain-sensitive 86Rb+ uptake was increased in arteries from DOCA-salt and renal hypertensive rats as compared to controls. In overnight-stored and 3-hour equilibrated aortic tissue, we then used low Na+ medium to reduce, or monensin, a Na+ ionophore, to increase total cell Na+, to study the relationship between cell Na+ and Na+-K+ pump activity. We observed a sigmoid relationship between total cell Na+ and ouabain-sensitive 86Rb+ uptake in tissue from all groups of rats. However, in tissue from DOCA-salt and renal hypertensive rats, the relationship between cell Na+ and pump activity was shifted, indicating a greater pump activity for each level of total cell Na+ and greater maximal pumping. These data suggest that increases observed in pump activity in in vitro arterial tissue from hypertensive rats may not be solely attributable to elevated cell Na+ content and may also involve increases in number of active sarcolemmal pump molecules per unit tissue weight or in their turnover rate.
Norepinephrine sensitivity and membrane potentials of caudal arterial muscle in DOCA-salt, Dahl, and SHR hypertension in rat.
Authors: Hermsmeyer K , Abel P W , Trapani A J
Published: August 2012

Comparison of norepinephrine (NE) sensitivity in caudal arterial muscle of rats with three forms of hypertension showed that there was no increase in either DOCA-salt or Dahl genetic hypertension, in contrast to the increased NE sensitivity found in spontaneously hypertensive rats (SHR). In hypertension induced by deoxycorticosterone acetate (DOCA)-salt treatment, as in Dahl genetic hypertension, there was also no difference in membrane potential (Em) between hypertensive and normotensive rats. By comparison to the SHR membrane alterations reported previously, any increased NE sensitivity might have been associated with altered Em electrogenesis which is triggered by a trophic factor of the sympathetic nervous system. SHR have a lower intracellular K+ free ion concentration and thus a smaller contribution of the ion gradient generated voltage which appears to be compensated for at rest by more active electrogenic ion transport. While SHR show greater depolarization and contraction than Wistar-Kyoto (WKY) rats in response to midrange NE concentrations, DOCA-salt and Dahl hypertensive rat caudal arterial muscle showed neither NE hypersensitivity nor any evidence of altered Em mechanisms. Ion transport in isolated peripheral arteries in DOCA-salt hypertension may only secondarily be altered in response to primary changes in humoral factors and altered neural control mechanism.
Immunohistochemical evidence that angiotensins I and II are formed by intracellular mechanism in juxtaglomerular cells.
Authors: Naruse K , Inagami T , Celio M R , Workman R J , Takii Y
Published: August 2012

The existence of angiotensin II (AII) immunoreactivity in juxtaglomerular (JG) cells of rat kidney, which has been demonstrated previously by immunohistochemical studies, can be explained either as the product of intracellular synthesis or by the internalization of receptor-bound AII originating in plasma. To resolve these two alternative mechanisms, attempts were made to identify AI in JG cells of rat kidney by immunohistochemical staining using specific antibodies to AI. Although AI-like immunoreactivity was not detected in normal rat kidney, rats treated with the angiotensin-converting enzyme inhibitors, MK-421 or captopril, showed AI-like immunoreactivity in JG cells. The presence of renin and AII-like immunoreactivity was demonstrated in the same cells by specific antibodies to respective antigens used on adjacent serial sections. These findings support an intracellular mechanism of the formation of AII and suggest an intracellular renin angiotensin system, presumably separate from the extracellular system.
Prostaglandin-related renin release from rabbit renal cortical slices.
Authors: Spokas E G , Wong P Y , McGiff J C
Published: August 2012

The possibility that 6-keto-prostaglandin E1 (6-keto-PGE1) affects renin release was studied using rabbit renal cortical slices, a preparation that eliminates hemodynamic, neural, and blood-borne factors that might influence renin release. The medium used for incubating the slices was collected for renin assay at the end of each of four successive 20-minute periods. Test agents were added only once, at the beginning of Period 3 (experimental period). Between Periods 3 an 4 (recovery period), the medium was aspirated and the slices rinsed with Krebs solution before replacing the medium. Renin release did not change in vehicle-treated slices. Unlike the PGI2-induced changes, the effects of 6-keto-PGE1 on renin release were sustained in Period 4. Indomethacin potentiated renin stimulation induced by 10 microM concentrations of PGI2 and 6-keto-PGE1 in Period 3 and by 6-keto-PGE1 in Period 4. Using platelet antiaggregatory activity as an index of stability, we found that PGI2 was largely inactivated within 10 minutes under the conditions used for incubating the slices (pH 7.4, 37 degrees C), while 6-keto-PGE1 was stable. The results lend further support to the concept that 6-keto PgE1 is capable of releasing renin through a direct action.
Dopamine modulates sodium-dependent aldosterone responses to angiotensin II in humans.
Authors: Drake C R , Carey R M
Published: August 2012

Studies have shown that dopamine inhibits angiotensin II (AII)-induced aldosterone secretion in bovine adrenal cells in vitro, but does not alter aldosterone responses to AII in sodium-replete normal humans. We investigated six normal men with plasma cortisol concentrations less than 2 micrograms/dl during oral administration of dexamethasone 0.5 mg every 6 hours for 2 days and in balance at 10 mEq sodium/day intake (UNa V 22 +/- 5 mEq/24 hr). The subjects received either dopamine 4 micrograms/kg/min or vehicle intravenously (i.v.) for 270 minutes on 2 consecutive days. After 120 minutes of dopamine infusion, AII was given in cumulative doses of 0.5, 1, 2, 4, and 6 pmol/kg/min i.v., each dose for 30 minutes. Control plasma aldosterone concentrations before vehicle or dopamine were 12 +/- 2 (mean +/- 1 SE) and 15 +/- 3 ng/dl, respectively. Aldosterone responses to AII were greater with vehicle than dopamine at AII doses of 4 and 6 pmol/kg/min (p less than 0.02). The slope of the AII-aldosterone dose-response curve was steeper with vehicle (0.36) than with dopamine (0.13), p less than 0.0001. Plasma renin activity and serum potassium concentrations were similar with vehicle and dopamine. Dopamine inhibits AII-induced aldosterone secretion during sodium deficiency in humans.
Atrial natriuretic factor inhibits angiotensin-, norepinephrine-, and potassium-induced vascular contractility.
Authors: Kleinert H D , Maack T , Atlas S A , Januszewicz A , Sealey J E , Laragh J H
Published: August 2012

We have previously shown that the natriuretic effect of rat atrial extract (AE) may be due, perhaps entirely, to its powerful renal hemodynamic actions. The present study was undertaken to test the hypothesis that mammalian atria contain a substance that behaves as a functional antagonist of endogenous vasoconstrictors, by examining the direct effects of AE and extensively purified atrial "natriuretic" factor on the contractile response of rabbit aortic rings to angiotensin II (AII), norepinephrine (NE), and K+-induced depolarization. Dose-response curves to AII and NE (i.e., change in tension vs log hormone concentration) were determined in the absence or presence of boiled AE or ventricular extracts (VE). Increasing concentrations of boiled AE caused a progressive right-ward shift of the AII and NE dose-response curves, whereas VE was without effect. A similar inhibitory effect was produced after extensive purification of atrial natriuretic factor by gel filtration and reversed-phase high performance liquid chromatography (HPLC). It appeared that this factor antagonized AII-induced contractility to a greater degree than that of NE. Moreover, the partially purified factor also inhibited the contraction induced by depolarization with 15 mM KCl in a concentration-dependent manner. These studies show that a substance present in the atria, but not ventricles, blocks both hormone- (receptor) and depolarization- (nonreceptor) induced vasoconstriction in aortic rings. Moreover, this antagonism is retained following extensive purification of an atrial factor that induces natriuresis in the intact rat and isolated rat kidney, suggesting that both the vasoactive and natriuretic properties of AE may reside in a single substance.(ABSTRACT TRUNCATED AT 250 WORDS)
Dahl S rats have increased natriuretic factor in atria but are markedly hyporesponsive to it.
Authors: Hirata Y , Ganguli M , Tobian L , Iwai J
Published: August 2012

Three experiments were carried out to determine whether atrial natriuretic factor (ANF) plays a part in Dahl hypertension. Results showed that ANF from both atria from 13 Dahl salt-sensitive (S) rats that had been fed a 4% NaCl diet for 12 weeks induced an average peak Na excretion of 23.0 muEq/min/g kidney in 13 Sprague-Dawley (SD) recipients vs 12.6 from atria from 13 salt-resistant (R) rats fed 4% NaCl (-45%, p less than 0.01), possibly indicating greater ANF secretion in S rats in order to enhance a reduced Na excretion. In 13 R rats, the ANF content in both atria increased from 14.0 after a 0.11% NaCl diet to 23.7 after 5 days of 4% NaCl diet (p less than 0.001) and then back to 12.6 after 12 weeks of 4% NaCl (p less than 0.001). Thus, ANF almost doubled after brief Na loading but returned to normal during continued Na loading. In S rats with a tendency to Na retention, ANF was elevated to about 23 in all three periods. ANF produced a 130-fold increase in natriuresis and a renal papillary plasma flow ( RPPF ) of 30.8 ml/min/100 g, 41% above the control level of 21.7, p less than 0.001. The marked increase in RPPF is very likely a partial cause of the natriuresis. A constant amount of ANF was continuously infused intravenously into 10 S rats and nine R rats all on 0.11% NaCl diets. Mean Na excretions in R and S were 5.3 and 4.6 muEq/min/100 g kidney before ANF.(ABSTRACT TRUNCATED AT 250 WORDS)
Effects of a specific inhibitor of the vascular action of vasopressin in humans.
Authors: Gavras H , Ribeiro A B , Kohlmann O , Saragoça M , Mulinari R A , Ramos O , Gavras I
Published: August 2012

Experimental evidence indicates that arginine vasopressin (AVP) may contribute to the rise of blood pressure (BP) in hypertension induced by renal failure and sodium overload. We studied the AVP inhibitor [1-(B-mercapto-B,B-cyclopentamethylenepropionic acid)-2-(O-methyl)tyrosine] AVP in 12 normal and seven hypertensive subjects with end-stage renal disease. To test the agent's capacity to block the pressor action of exogenous AVP In humans, we constructed a dose-response curve with AVP doses of 1 to 20 mU/kg, raising BP by up to 30 mm Hg. Subsequently, five volunteers receive intravenous (i.v.) doses of 0.1 mg, and five volunteers received 0.5 mg of the inhibitor. The dose-response curve was then repeated with AVP doses up to 200 mU/kg. Both doses of the inhibitor shifted the curve to the right and downward, with the BP response to 20 mU/kg AVP being inhibited by 23% and 80% respectively. The duration of action of the compound was tested in two additional subjects, and was found to be over 3 hours. We then tested the compound in seven hypertensive patients with end-stage renal failure. Two days before dialysis, patients received a 150 mEq/day Na diet. After an additional Na load of 180 mEq via i.v. saline over 3 hours under constant BP and ECG monitoring, they received an i.v. bolus of 0.5 mg AVP inhibitor. A moderate BP fall occurred in five patients; it was maximal at 45 to 60 minutes and returned to baseline by 70 to 90 minutes.(ABSTRACT TRUNCATED AT 250 WORDS)
Free calcium concentration in platelets closely relates to blood pressure in normal and essentially hypertensive subjects.
Authors: Erne P , Bürgisser E , Bolli P , Ji B H , Bühler F R
Published: August 2012

Calcium has been implicated in smooth muscle contraction, arterial resistance, and the pathophysiology of essential hypertension. Using the intracellularly trapped fluorescent dye quin2 , the free calcium concentration in platelets was found to be elevated in patients with borderline (n = 8, p less than 0.01) and established essential hypertension (n = 23, p less than 0.001) when compared with normotensive subjects (n = 30). There was a close correlation between intracellular free calcium and systolic blood pressure (n = 61, r = 0.882, p less than 0.001) as well as diastolic blood pressure (n = 61, r = 0.950, p less than 0.001). The slopes of the regression lines did not differ between the groups.
Malignant hypertensive crisis induced by chronic intrarenal norepinephrine infusion.
Authors: Lohmeier T E , Tillman L J , Carroll R G , Brown A J , Guyton A C
Published: August 2012

The purpose of the present study was to develop a controllable experimental model in the dog that would consistently and predictably produce a malignant hypertensive crisis, and to determine the sequential changes in renal function, salt and water balance, and hormones that are involved in the transition from benign to accelerated hypertension. Norepinephrine (NE) was infused continuously into the renal artery of unilaterally nephrectomized dogs that were maintained on 50 mEq sodium/day. The infusion rate of NE was increased each day according to the following schedule: 0.05, 0.1, 0.2, 0.3, 0.4, and 0.5 microgram/kg/min. During the first 4 to 5 days of intrarenal NE infusion, there was a progressive decrease in glomerular filtration rate (GFR) and effective renal plasma flow (ERPF), and increases in plasma renin activity (PRA), mean arterial pressure (MAP), and filtration fraction. At the end of this period of benign hypertension, MAP had risen from a control value of 91 +/- 4 to 132 +/- 8 mm Hg, in association with approximately a 10-fold increase in PRA and a 40% reduction in renal function. Then, suddenly, during the subsequent 24-hour infusion period, the MAP increased abruptly in all animals (MAP = 156 +/- 8 mm Hg), and a hypertensive crisis occurred. This crisis was associated with the following: salt and water depletion, hyponatremia, hypovolemia and hemoconcentration, polydipsia, marked activation of the renin-angiotensin-aldosterone system, increased plasma cortisol concentration, hemolysis, marked impairment in renal function, lethargy, and vomiting.(ABSTRACT TRUNCATED AT 250 WORDS)
Separation of peripheral dopamine receptors by a selective DA1 antagonist, SCH 23390.
Authors: Goldberg L I , Glock D , Kohli J D , Barnett A
Published: August 2012

Intravenous (i.v.) infusions of SCH 23390 (R-(+)-8-chloro-2,3,4,5-tetrahydro-3-methyl-5-phenyl-1H-3-benzazepine-7- ol) produced dose-related antagonism of dopamine (DA)-induced renal vasodilation in phenoxybenzamine-treated dogs at infusion rates of 0.05, 0.15, and 0.5 microgram/kg/min. The highest rate of infusion, 0.5 microgram/kg/min, resulted in pronounced antagonism of this DA1-receptor-mediated response. In contrast, a 10 times higher infusion rate, 5 micrograms/kg/min, did not antagonize the following DA2-mediated responses: increase in femoral blood flow produced by apomorphine and piribedil in untreated dogs; and N,N-di-n-propyl DA (DPDA)-induced inhibition of the tachycardia produced by cardiac accelerator nerve stimulation. Infusions of 0.5 micrograms/kg/min or greater of SCH 23390 did not affect the actions of agonists of alpha1-, alpha2-, beta1-, and beta2-adrenergic, histamine, serotonin, and cholinergic receptors, or the vasodilation produced by bradykinin. At the infusion rates used in these studies, SCH 23390 did not affect arterial blood pressure or heart rate. These data indicate that SCH 23390 is the most specific and selective antagonist of DA1 receptors thus far described. Accordingly, SCH 23390 should be extremely useful in investigations of potential physiological and pathological roles of DA and in the classification of DA receptors.
Decreased isoproterenol-induced "down"-regulation of beta-adrenergic receptors in the myocardium of SHR.
Authors: Limas C J , Limas C
Published: August 2012

The number of cardiac beta-adrenergic receptors and the activity of isoproterenol-stimulated adenylate cyclase are lower in spontaneously hypertensive rats (SHRs) and may account for diminished inotropic responsiveness to beta-agonists. Differences in isoproterenol-induced desensitization of the cardiac adenylate cyclase system between 14- to 16-week-old SHRs and Wistar-Kyoto (WKY) controls were studied using cardiac membranes, isolated cardiac myocytes, and intact animals. In both animal strains, the isoproterenol-induced "loss" of beta-adrenergic receptors in the cardiac membranes required adenosine triphosphate (ATP), magnesium (Mg2+), and guanosine 5'-triphosphate (GTP). The ATP and Mg2+ requirement may reflect a crucial role for a phosphorylation step, since desensitization was prevented by cordycepin, a nonspecific phosphorylation inhibitor. In both isolated myocytes and intact animals, isoproterenol induced a redistribution of the beta-adrenergic receptors (but not of adenylate cyclase) from the cell membrane to the cytosol. Internalization of the receptors was not secondary to the loss of membrane fragments to the cytosol, since the receptors sequestered in a fraction devoid of cell surface markers. In all three preparations, the extent of isoproterenol-induced "loss" of beta-receptors and isoproterenol-stimulated adenylate cyclase was considerably lower in SHRs than WKYs. This difference appeared to be due to a reduced capacity of isoproterenol to induce translocation of beta-receptors from the membranes to the cytosol of SHRs, because of a change in the physical properties of either the beta-receptors themselves or the membranes into which they were embedded.
Propylbutyldopamine. Mechanism of blood pressure lowering in hypertensive patients.
Authors: Taylor A A , Fennell W H , Ruud C O , Pool J L , Nelson E B , Ginos J Z , Mitchell J R
Published: August 2012

The effects of propylbutyldopamine ( PBDA ), an analog of dopamine lacking significant vasoconstrictor effects, were examined in seven patients with essential hypertension. Cardiovascular hemodynamics, renal plasma flow, urinary sodium excretion, and the renin-angiotensin-aldosterone system were examined during PBDA infusion both before and after administration of low (8 micrograms/kg) and high (40 micrograms/kg) doses of the dopamine receptor antagonist metoclopramide. Infusion of PBDA at a rate of 20 micrograms/kg/min lowered mean arterial pressure from an average control value of 112 +/- 4 to 94 +/- 3 mm Hg during the last 5 minutes of infusion (p less than 0.01), and increased effective renal plasma flow from 330 +/- 22 ml/min to 591 +/- 46 ml/min (p less than 0.01). Changes in heart rate (+ 16% +/- 5% increase from control values of 77 +/- 3 bpm), urinary sodium excretion (+ 13% +/- 5% increase from control value of 121 +/- 11 muEq/min), plasma renin activity (+ 23% +/- 15% increase over control value of 1.3 +/- 0.3 ng angiotensin I/ml/hr), and plasma aldosterone (+ 26% +/- 12% increase over control value of 17 +/- 6 ng/dl) accompanied PBDA infusion. Pretreatment with metoclopramide at a dose of 8 micrograms/kg prior to PBDA infusion partially blunted the blood pressure reduction produced by PBDA alone (-10% +/- 8% vs -20% +/- 4% compared to control values, p less than 0.1) but had no effect on PBDA -induced increases in renal plasma flow (+ 179% +/- 15% vs + 179% +/- 9% compared to control).(ABSTRACT TRUNCATED AT 250 WORDS)
Brief historical background and principal nature of process.
Authors: Folkow B
Published: August 2012

After a brief outline of the historical background, the biological principle of structural tissue adaptation to alterations in load is discussed with special reference to the cardiovascular system. It is stressed that adaptive changes of cardiac and vascular design to local load are rapid, precise, and, on the local level, highly appropriate. However, in hypertension, when they affect the entire systemic resistance section (structural autoregulation), as well as some major "barostats," an upward structural resetting of the entire pressure equilibrium occurs. Further, by way of the consequent vascular resistance vessel hyperreactivity, a positive feedback interaction is established with functional pressure effects and thus tends to further escalate the pressure rise. For these reasons the "normal" structural factor becomes of key importance for the initiation, maintenance, and gradual aggravation of chronic high pressure states.
Consequences of structural renovascular changes for renal barostat function.
Authors: Folkow B , Göthberg G
Published: August 2012

During maximal vasodilatation the renal vascular beds of normotensive control rats (NCR), uninephrectomized NCR (U-NCR), spontaneously hypertensive rats (SHR), and two-kidney, one clip renal hypertensive rats (RHR) have been compared concerning glomerular filtration capacity, total renovascular resistance, and the relationship between perfusion pressure and glomerular filtration rate (GFR). The GFR reflects the important ratio between the preglomerular and postglomerular resistances that is a major determinant of GFR, and during maximal vasodilatation it shows whether, and how, this ratio is altered by differentiated renovascular structural adaptation. In SHR hypertension this ratio soon becomes increased to match the pressure rise as a result of structural changes, which implies a most efficient upward resetting of the renal barostat function. Later the postglomerular resistance is also raised in SHR as a result of structural changes. This adaptation presumably occurs to offset the gradual deterioration in glomerular filtration capacity. In the clipped, "low-pressure" RHR kidney, only the preglomerular resistance is reduced, a local adaptation tending to offset the effect of the artificial inflow hindrance on GFR as a result of structural changes. In the "pressure-exposed" RHR kidney the preglomerular and postglomerular resistances are both equally increased, again as a result of structural changes. In this situation, therefore, resetting of the renal barostat function occurs less efficiently than in SHR. This may explain the observation that arterial pressure readily normalizes in RHR on declipping. The hypertrophic U-NCR kidney shows a proportional and uniform outgrowth of the renovascular bed, thus without altering the pre-postglomerular resistance ratio.(ABSTRACT TRUNCATED AT 250 WORDS)
Structural adaptation in borderline hypertension.
Authors: Sivertsson R
Published: August 2012

Animal studies have shown that the cardiovascular system adapts to blood pressure elevation very early in the development of hypertensive disease. This discussion is concerned with structural adaptation in mild or borderline hypertension in humans. A literature review is given, followed by some preliminary data from a current hemodynamic follow-up study on young individuals with mild blood pressure elevation. Hand blood flow at maximal vasodilatation was studied plethysmographically, the baroreceptor reactivity was investigated by analyzing heart rate after intravenously administered angiotensin, and the left ventricle wall thickness was evaluated with M-mode echocardiography. The results indicate that the resistance vessels, the high-pressure baroreceptors, and the left ventricle of the heart are structurally modified even in very mild blood pressure elevation.
Structural changes of large arteries in sustained essential hypertension.
Authors: Safar M E , Simon A C , Levenson J A
Published: August 2012

The physical properties of intact superficial arteries can be studied in humans by using original pulsed Doppler systems. Measurements of the diameter, blood flow velocity, volumic flow, and compliance of the brachial artery can be obtained in hypertensive humans in comparison with controls of the same age. In sustained essential hypertension, arterial compliance is decreased, in a manner that is not related exclusively to age and to the level of blood pressure. On the basis of pharmacological studies, the predominant role of activation of the autonomic nervous system can be excluded. As observed in isolated systolic hypertension and in arteriosclerosis obliterans of the lower limbs, the reduction in arterial compliance is probably due to structural alterations of the arterial wall, which produce a disproportionate increase in systolic pressure. Nitroglycerine is able to reverse both the decreased compliance and the increased systolic pressure. The conclusion follows that adaptive changes of large arteries participate in the structural autoregulation of blood flow in hypertension and lead to a predominant elevation of systolic pressure in older subjects.
Circulatory changes in muscle and skin arteries in primary hypertension.
Authors: Clement D L , Duprez D
Published: August 2012

This review deals with circulatory adjustments occurring in the limb arteries of hypertensive patients. Measurements of regional blood flow are mandatory, because conclusions drawn from calculated total peripheral resistance often are not applicable to local vascular beds. Limb arteries, which can be followed by easy and noninvasive methods, often are the first choice for study of regional circulation. In this discussion, a few historic studies are cited first; next, the data available on skeletal muscle (forearm and calf) and skin (finger) circulation are reviewed, to show that flow through both muscle and skin is increased in mild and moderate hypertension, while there is a trend to lower values in more severe hypertension. Our own data are derived from 51 untreated patients showing mild to moderate hypertension, matched to 23 normotensive subjects. Flow is measured simultaneously with an ECG-triggered venous occlusion plethysmograph at calf and finger. At rest, calf and finger blood flows are significantly higher and calculated resistance is lower in hypertensive subjects; during reactive hyperemia, blood flow remains higher in hypertensive subjects but calculated resistance increases up to values that are higher, compared to normotensive control subjects; these data are compatible with structural changes in the vascular wall.
Regression of retinal vascular changes by antihypertensive therapy.
Authors: Bock K D
Published: August 2012

The features of hypertensive retinal arterial vessel changes and their sequelae are reviewed. General or focal narrowing, increased reflexes or abnormal arteriovenous crossings, are often associated with, but not specific for, hypertension. They persist, with very rare exceptions, even after long-term successful antihypertensive therapy. Papilledema, cotton-wool spots, hemorrhages, and fatty exudates in malignant hypertension disappear completely within 6 to 12 months if blood pressure is well controlled. Inadequate control of elevated blood pressure delays, but does not prevent, the regression of retinopathy. The reversal into the "benign" phase may continue for years, even if blood pressure control worsens. This may be explained by a regain of autoregulation which allows the arteriolonecrotic lesions to heal. According to their size, retinal arteries are representative of the target organ of hypertensive small vessel disease. They supply a tissue that is highly sensitive to ischemia. However, even long-standing nonmalignant hypertension seems not to damage retinal tissue.