bluuebunny/crossref_metadata_2025 huggingface dataset:
The role of vasopressin in blood pressure maintenance in diabetic orthostatic hypotension.
Authors: Saad C I , Ribeiro A B , Zanella M T , Mulinari R A , Gavras I , Gavras H
Published: September 2013

The purpose of these studies was to assess the role of vasopressin in maintaining supine and upright blood pressures in hypertensive diabetic subjects. Patients with (n = 6) or without (n = 10) evidence of autonomic insufficiency had blood pressure and heart rate monitored before and after receiving an intravenous injection of 0.5 mg of a V1 vasopressin inhibitor. None of the patients had supine changes in blood pressure or heart rate. However, upon assuming the erect position, the six patients with preexisting orthostatic hypotension had an average blood pressure fall of 44 mm Hg after vasopressin inhibition (as opposed to 20 mm Hg before), accompanied by a modest rise in heart rate of 20 beats/min. Those without autonomic dysfunction were separated into two subgroups. Four developed an average fall in orthostatic blood pressure of 18 mm Hg after vasopressin inhibition, whereas the remaining six had no change. There were no distinguishing hormonal characteristics (vasopressin, renin, and catecholamine levels) between the groups, but in the patients with autonomic dysfunction, the renin level failed to rise when upright. We conclude that vasopressin plays an important role in preventing or minimizing orthostatic hypotension in diabetic patients. Its pressor contribution is crucial in those with autonomic insufficiency and impaired renin and sympathetic responses, in whom the pressor effectiveness of vasopressin is greatly enhanced.
Clinical pharmacology of calcium antagonists. Satellite symposium on calcium antagonists.
Authors: Frohlich E D
Published: September 2013

A new class of agents has been made available for the treatment of hypertension. These calcium antagonists have rapid bioavailability and dramatic antihypertensive effects through reduction of total peripheral resistance and the vascular resistance of the major target organs of the body. These changes are usually associated with unchanged cardiac output, preserved organ blood flows, maintained organ function, and preserved reflex responses without fluid retention in long-term treatment. These drugs do not stimulate plasma renin activity and aldosterone levels. Thus they fulfill many of the major criteria for an ideal antihypertensive agent.
The atrial natriuretic factor in hypertension. State of the art lecture.
Authors: Genest J , Larochelle P , Cusson J R , Gutkowska J , Cantin M
Published: September 2013

Studies were conducted to assess the effects of bolus injections and infusions of human atrial natriuretic factor (ANF) in control subjects and patients with mild essential hypertension, and to measure plasma immunoreactive ANF (irANF) concentration in a large group of patients with essential hypertension. The results are compared with those obtained by other groups on the measurements of plasma irANF in hypertensive patients. It appears that plasma irANF concentrations are not increased in patients with mild essential hypertension despite the evidence of increased preload and of atrial distention as reported by others. This suggests a hyporesponsiveness of the atria to release ANF.
Evaluating hyperfiltration with glycine in hypertensive rats with renal ablation.
Authors: Herrera-Acosta J , Tapia E , Bobadilla N A , Romero L , Cermeño J L , Alvarado J A , Gabbai F B
Published: September 2013

Hypertension-induced renal damage is mediated by increased glomerular pressure and flow. These alterations have been evaluated by the renal response to protein or amino acids. To test this assumption, we studied glomerular hemodynamic responses to glycine infusion in rats with reduced renal mass, with and without Goldblatt hypertension. The left kidney was ablated by two thirds in 12 rats, and in 5, hypertension was induced by clipping the right renal artery. Seven normal, unmanipulated rats served as controls. Micropuncture was performed in the left kidney during control and 15% glycine infusion periods, 45 days after surgery. Arterial pressure was higher in hypertensive rats (160.3 mm Hg) than in controls (103.8 mm Hg) and rats with renal ablation (125 mm Hg; p less than 0.05). Higher values of single-nephron glomerular filtration rate and single-nephron plasma flow in rats with renal ablation (63.0, 223.7 nl/min) and hypertension (46.1, 239.7 nl/min) than in controls (28.8, 94.9; p less than 0.05) demonstrated the presence of hyperfiltration. However, glomerular pressure was elevated only in hypertensive rats (40.1 mm Hg), when compared to controls (32.7 mm Hg; p less than 0.05) and rats with renal ablation (33.4 mm Hg; p less than 0.05). Glycine increased single-nephron glomerular filtration rate and single-nephron plasma flow in control rats by 76 and 65%; rats with renal ablation had only partial responses, 35% and 23%, respectively, whereas in hypertensive rats the response was completely abolished. Glycine detected hyperfiltration and unmasked a dysfunction of preglomerular vessels that was greater in hypertensive rats and could contribute to the rise in glomerular pressure and flow and thereby to glomerular damage.
Angiotensin analogues that selectively augment the force of contraction of the isolated heart.
Authors: Khosla M C , Bachynsky E , Forgac S , Lakios-Cherpas C , Bumpus F M
Published: September 2013

Angiotensin II (Ang II) produces a positive inotropic effect on the heart; however, its usefulness as an inotropic agent is limited because of its inherent vasoconstrictor action. We therefore designed Ang II analogues that are potent, positive inotropic agents with minimal myotropic properties. Replacement of the proline residue in position 7 with alanine reduced the pressor and vascular contractile response to less than 1% of Ang II. In spite of negligible vascular actions, however, [7-alanine]Ang II produced 50% of the inotropic activity of Ang II in the cat papillary muscle. The results of pharmacological evaluation of various position 7-substituted analogues were as follows: 1) Replacement of proline in position 7 of angiotensin I (Ang I) and Ang II with primary amino acids produced cardiac-specific, positive inotropic properties. 2) The selectivity of positive cardiac inotropic activity of position 7-substituted analogues of Ang II was dependent upon the nature of the amino acid in position 1. Replacement of aspartic acid in position 1 with sarcosine increased vasoconstrictor activity, thereby diminishing cardiac selectivity. However, this change did not affect cardiac selectivity in Ang I analogues. 3) Introduction of any type of steric hindrance in position 7 (e.g., replacement of alanine with N-methyl- or alpha-methylalanine) led to a considerable loss in inotropic activity. In conclusion, contrary to rigid, structural requirements (solution conformation) for the pressor action of Ang II, a less organized structure or a random conformation at the carboxyl terminus appears to favor cardiac-selective contractile response (or positive inotropic response).
Brain renin-angiotensin. Central control of secretion of atrial natriuretic factor from the heart.
Authors: Itoh H , Nakao K , Yamada T , Morii N , Shiono S , Sugawara A , Saito Y , Mukoyama M , Arai H , Imura H
Published: September 2013

To elucidate the modulatory role of the brain renin-angiotensin system in the regulation of the secretion of atrial natriuretic factor (ANF) from the heart, the effects of intracerebroventricular administration of angiotensin II on the plasma ANF level were examined in conscious unrestrained rats. Administration of angiotensin II in doses of 100 ng and 1 microgram significantly enhanced ANF secretion induced by volume loading with infusion of 3 ml of saline (peak values of the plasma ANF level: control, 220 +/- 57 pg/ml; angiotensin II 100 ng, 1110 +/- 320 pg/ml, p less than 0.01; angiotensin II 1 microgram, 1055 +/- 60 pg/ml, p less than 0.01). Injection of angiotensin II alone had no significant effect on the basal plasma ANF level. Central angiotensin II-induced ANF secretion was significantly attenuated by pretreatment with intravenous administration of the V1-receptor antagonist of vasopressin or intracerebroventricular administration of phentolamine. These results indicate that the brain renin-angiotensin system modulates ANF secretion in response to volume loading through the stimulation of vasopressin secretion or the activation of the central alpha-adrenergic neural pathway.
Site of entry of kininase II into renal tubular fluid.
Authors: Cardini J F , Santos R A , Martins A S , Machado R P , Alzamora F
Published: September 2013

The stop-flow technique was used to determine the site of entry of kininase II into tubular fluid in dogs. Stop-flow patterns were constructed for kininase II, p-aminohippurate, sodium, and potassium. The proximal tubule was localized by the peak of p-aminohippurate concentration and the distal tubule by the minimum sodium concentration. In the stop-flow pattern for kininase II, three peaks (a, b, and c) were observed. A main peak (a), located 2.25 +/- 0.45 ml distal to the p-aminohippurate peak (p less than 0.01) and 3.75 +/- 0.31 ml proximal to the minimum sodium concentration (p less than 0.001), was observed in all experiments. Peak c, located 2.6 +/- 0.4 ml (p less than 0.01) proximal to the p-aminohippurate peak, was observed in five dogs. Peak b appeared in five dogs and was always located 2.0 ml distal to the minimum sodium concentration. This peak was coincident with the potassium peak. Only two of eight experiments showed all three peaks. These results showed that the major kininase II entry into the tubular fluid is near the p-aminohippurate peak and that distal entry occurred in 63% of the dogs.
Diuresis and natriuresis during continuous dopamine-1 receptor stimulation.
Authors: Hughes J M , Ragsdale N V , Felder R A , Chevalier R L , King B , Carey R M
Published: September 2013

Stimulation of renal dopamine-1 (DA1) receptors for 3 hours produces an increase in renal plasma flow and sustained natriuresis. The present study was designed to assess the response of renal hemodynamic and tubular function to long-term DA1 receptor stimulation. Fenoldopam, a selective DA1 receptor agonist, was infused intravenously for 24 hours in 10 normal male subjects in metabolic balance at 150 mEq sodium and 60 mEq potassium intake in a single-blind, vehicle-controlled protocol. During DA1 receptor activation, urine flow rate and fractional excretion of sodium increased for the first 5 hours, 16.9 +/- 0.9 ml/min compared with a vehicle control value of 12.4 +/- 0.5 ml/min (p less than 0.001) and 2.0 +/- 0.1% compared with a vehicle control value of 1.1 +/- 0.1% (p less than 0.005), respectively. Urinary sodium excretion rose at 5 hours, 0.27 +/- 0.02 mEq/min compared with a vehicle control value of 0.14 +/- 0.01 mEq/min (p less than 0.01). Renal plasma flow increased during fenoldopam at 5 hours, 505 +/- 47 ml/min compared with a vehicle control value of 397 +/- 25 ml/min (p less than 0.01), and was sustained for 24 hours, 523 +/- 40 ml/min compared with 432 +/- 31 ml/min (p less than 0.05). The distal sodium load increased and the percentage of distal sodium reabsorption decreased during fenoldopam. Glomerular filtration rate, blood pressure, heart rate, plasma aldosterone concentration, plasma renin activity, and fractional excretion of potassium were unchanged. Selective DA1 receptor activation produced sustained 5-hour diuresis and 11-hour natriuresis without kaliuresis or a systemic hemodynamic effect.(ABSTRACT TRUNCATED AT 250 WORDS)
Baroreceptor reflex modulation by vasopressin microinjected into the nucleus tractus solitarii of conscious rats.
Authors: Michelini L C , Bonagamba L G
Published: September 2013

To determine whether the central vasopressinergic system at the level of nucleus tractus solitarii (NTS) modulates the reflex control of heart rate, we employed a new method for microinjection into the brainstem of conscious, freely moving rats. Baroreceptor reflex function was assessed during pressure changes induced by intravenous administration of phenylephrine (0.25-8 micrograms/kg) and sodium nitroprusside (0.5-16 micrograms/kg) in rats microinjected, through a permanent cannula into the brainstem, with saline, arginine vasopressin (AVP), or an AVP blocker. Baseline levels of pressure and heart rate were not changed by either peptide pretreatment. Restricted injection of AVP (20 ng-0.2 microliter) into the NTS attenuated the reflex bradycardia during pressure increases, with an upward displacement of the baroreceptor reflex function line (p less than 0.01) without change in the sensitivity. Local blockade of endogenous AVP, d(CH2)5Tyr(Me)AVP (1 microgram-0.2 microliter), depressed baroreceptor reflex sensitivity with intense bradycardia to either small or large pressure increases. Baroreceptor reflex control of heart rate in response to decreases in pressure was preserved during pretreatment with AVP, whereas endogenous blockade of AVP increased baroreceptor reflex sensitivity. These effects were specific to the NTS, since in another four rats there were no effects when the injections were made 1 mm above, into the cerebellum. The changes in baroreceptor reflex control of heart rate in conscious, unrestrained rats caused by administration of AVP and its endogenous blockade provide evidence that central vasopressinergic synapses at the NTS are important physiological modulators of baroreceptor reflex function.
Diuretics and their side effects. Dilemma in the treatment of hypertension.
Authors: Weinberger M H
Published: September 2013

Diuretics have traditionally been the keystone of antihypertensive therapy. A variety of clinical trials, designed to examine the benefit of blood pressure reduction in decreasing morbidity and mortality from hypertension-related cardiovascular disease, have surprisingly failed to show a decrease in coronary artery disease death rate, although other forms of vascular disease were impressively reduced. These trials have consistently used diuretics as the initial therapeutic choice. Such observations have stimulated a reevaluation of the "stepped-care" approach and a critical appraisal of diuretic effects. This review examines the efficacy of diuretics in reducing blood pressure and attempts to identify individuals most likely to respond to these agents. The side effects of diuretic therapy are reviewed in hemodynamic, cardiac, metabolic, and symptomatic terms, but because some of these aspects of diuretic or antihypertensive therapy are detailed elsewhere in this monograph, the present discussion focuses on cardiac, metabolic, hemodynamic, and symptomatic effects. Finally, alternative therapeutic options and guidelines for therapy are outlined.
Antagonism of antihypertensive drug therapy by nonsteroidal anti-inflammatory drugs.
Authors: Oates J A
Published: September 2013

Certain nonsteroidal anti-inflammatory drugs antagonize the action of antihypertensive therapy. Indomethacin has been shown to abrogate the antihypertensive effect of beta-adrenergic receptor blockers, diuretics, converting enzyme inhibitors, and several antihypertensive drug combinations, and the accumulated evidence on piroxicam indicates that it also raises arterial pressure in treated patients. In contrast, sulindac and aspirin do not reverse the effects of antihypertensive drugs, and currently available data indicate that they are the safest cyclooxygenase inhibitors for use in hypertensive patients. In the absence of definitive information on the array of other nonsteroidal anti-inflammatory drugs, they should be considered to pose a risk similar to indomethacin until proved otherwise. The magnitude of the elevation in blood pressure varies between patients, ranging from no effect to dangerous hypertensive responses. Generalized inhibition of the cyclooxygenase enzyme has opposing effects on arterial pressure, lowering renin on one hand and causing sodium retention on the other. Some evidence suggests that cyclooxygenase inhibition causes the greater increments in pressure in patients who initially have low plasma renin activity (often the elderly). The potential for cerebral vascular catastrophes attends these drug interactions in which platelet function also is suppressed by cyclooxygenase inhibition.
Classification of resistant hypertension.
Authors: Frohlich E D
Published: September 2013

Resistant hypertension has become a less frequently encountered clinical problem. It may be defined as failure to control pressure below levels of 160/100 mm Hg despite adequate nonpharmacological intervention and pharmacotherapy. Adequate therapy is defined as the use of three antihypertensive agents, which includes a diuretic plus two other compounds. Resistant hypertension may be classified as physician resistant, patient resistant, and hypertension resistant. Each of these categories is described, and resolution of the problem of resistance can usually be achieved by improved patient education and adherence to therapy, reevaluation of diagnosis, and consideration of alternative therapeutic programs.
Phenylpropanolamine and other over-the-counter vasoactive compounds.
Authors: Bravo E L
Published: September 2013

Phenylpropanolamine is a sympathomimetic amine that shares structural similarities with amphetamine and ephedrine. It increases blood pressure primarily by increasing peripheral vascular resistance. This effect is the result of alpha-adrenergic agonist activity largely from both direct stimulation of adrenergic receptors and release of neuronal norepinephrine. As such, it has the potential to interact with other drugs to produce toxic reactions, especially in treated hypertensive patients. Complications have occurred with single oral doses that suggest some normal subjects may be more sensitive to the drug than others. The incidence of serious complications in the general population is small but could be much higher in susceptible individuals (e.g., cardiomyopathic and hypertensive patients). The availability of high-dose phenylpropanolamine-containing preparations without medical supervision is potentially dangerous, and certain restrictions should be imposed on such preparations.
Prevalence of drug resistant hypertension.
Authors: Alderman M H , Budner N , Cohen H , Lamport B , Ooi W L
Published: September 2013

Hypertension patients (1781), drawn from seven large employee groups in and around New York City, were studied to determine the prevalence of resistant hypertension among them. The blood pressure criteria for resistance (potential resistance) were failure to reach and maintain a blood pressure less than 160/95 mm Hg on two separate occasions during at least 1 year of treatment. Confirmed resistance required that during the same period of follow-up, in which at least two antihypertensive agents had been prescribed simultaneously, blood pressure control had not been achieved. Potential resistance during 1 year of treatment was found in 75 patients (4.2%), and confirmed resistance for the same period was found in 52 patients (2.9%). Diastolic resistance was far more common than systolic; the systolic/diastolic resistance was the rarest of all. Of the 52 patients with confirmed resistance for the first year, 33 achieved control in subsequent years. In sum, true resistance as defined by rigorous criteria pertaining to the hypotensive effects of pharmacological intervention in the general population is exceedingly rare.
Factors contributing to resistant hypertension. Cardiac considerations.
Authors: Fouad-Tarazi F M
Published: September 2013

Medical treatment of hypertension has beneficial effects in the prevention of complications of the disease and in prolongation of survival. Nevertheless, the control of hypertension may sometimes be difficult. In this respect, the heart itself may interfere with blood pressure control because of increased cardiac output or because of cardiogenic reflexes that could conceivably not only initiate but also perpetuate peripheral vasoconstriction. The resultant persistence of hypertension may induce further cardiac changes that will in turn perpetuate the rise in blood pressure.
Factors that contribute to resistant forms of hypertension. Pharmacological considerations.
Authors: Johns D W , Peach M J
Published: September 2013

Treatment failure may be caused by induction of compensatory mechanisms that compromise effectiveness of the antihypertensive regimen. Antihypertensive agents have been classified according to mechanism of action, and compensatory mechanisms usually evoked by each class of drugs have been reviewed. Host factors may be responsible for the inability to control blood pressure or may predict special sensitivity or contraindication to a particular class of antihypertensive agents. Recommendations have been made for modification of stepped-care regimens and selection of initial antihypertensive agents based on host factors. Experimental evidence suggests the ability to target antihypertensive therapy in a manner that will prevent or reverse specific end-organ damage. Clinical studies are needed to define the long-term benefit derived from aggressive target organ protection.
Blood pressure monitoring outside the office for the evaluation of patients with resistant hypertension.
Authors: Pickering T G
Published: September 2013

Although severe hypertension is associated with a poor prognosis, there exists a substantial number of patients who have persistently elevated blood pressures, but no signs of target organ damage, and nearly normal life expectancy. In such cases, measurement of blood pressure outside the clinic may give readings that are as much as 30 mm Hg lower than the clinic readings. The first step recommended in the identification of such patients is to use home blood pressure monitoring. If home blood pressures are low, 24-hour ambulatory blood pressure recording is indicated. If this also gives low readings, it is appropriate to treat patients according to their level of home blood pressure. Because of the unreliability of clinic pressures, ambulatory and home blood pressure monitoring may also be of value in assessing the response to treatment.
Effects of tonin, an angiotensin II-forming enzyme, on vascular smooth muscle in the normal rabbit.
Authors: Garcia R , Schiffrin E L , Thibault G , Genest J
Published: September 2013

Tonin is an enzyme of the serine protease family present in different rat tissues which releases angiotensin II (AII) directly from angiotensinogen and the tetradecapeptide renin substrate and from angiotensin I (AI). Tonin potentiates the effect of norepinephrine (NE) in the rat mesenteric artery preparation and in the aortic strips from normal and hypertensive rats. In rabbit aortic and mesenteric artery strips tonin potentiates the effect of NE, almost doubling its response. A similar effect was observed on the KCl and AII-induced contraction. This tonin-induced potentiation is reversible and long-lasting, persisting for 1 to 2 hours after being added into the tissue bath. In 75% of the vascular strips assayed, tonin elicited a contraction with a short latency period and with a maximum tension ranging from a few milligrams to over 1 g. To clarify the mechanisms of tonin effect on vascular smooth muscle, a variety of agents have been used. Neither indomethacin, saralasin, nor alpha- or beta-adrenergic blockers changed the direct contraction or the potentiation induced to NE. Db-cAMP and theophylline blocked the potentiation to the response to NE. A Ca2+-free medium, La3+, and verapamil produced a 75% inhibition of the direct tonin-induced contraction. Papaverine, isoproterenol, and theophylline relaxed the same contraction. Enzymatic inactivation of tonin blocked completely the direct contraction but not the potentiation to NE. These experiments suggest that the vasoactive effect of tonin may be mediated by the release of intracellular-bound calcium, an effect dependent on a proteolytic effect of tonin, and by increasing the cellular permeability to calcium, which is not of a proteolytic effect. It is suggested that tonin remains attached to the vascular strips by mechanisms as yet not clarified.
Alkyl ether analogs of phosphatidylcholine are orally active in hypertensive rabbits.
Authors: Muirhead E E , Byers L W , Desiderio D , Smith K A , Prewitt R L , Brooks B
Published: September 2013

1-0-alkyl ethers of phosphatidylcholine having an acetoyl in the second position were derived from fresh renal tissue. The main ether so derived had a 16:0 chain. The C16:0 alkyl ether was synthesized de novo. The renally derived and the synthetic ether exerted a similar and powerful antihypertensive action in hypertensive rabbits when given orally in divided doses. This action was prolonged, requiring more than 60 hours after the last input of the compound for recovery of the arterial pressure. As these ethers exerted their antihypertensive action, there was no evidence of adverse effects. Noteworthy was the failure of these depressor compounds to cause renin release. Diuresis-kaliuresis did not occur. A suggestion of sodium retention was noted.
Potassium feeding reduces hyperactive central nervous system pressor responses in Dahl salt-sensitive rats.
Authors: Goto A , Tobian L , Iwai J
Published: September 2013

Dahl showed that feeding KCl prevents the rise in blood pressure caused by a high NaCl diet in salt-sensitive Dahl "S" rats. Such S rats when normotensive on a low NaCl diet have a 2 to 3 times greater pressor response than Dahl "R" rats to intracerebroventricular hypertonic saline (600 mOsm/liter) or angiotensin II (AII) (500 ng). Does dietary KCl prevent NaCl hypertension in S rats partly by abolishing these hyperactive central nervous system (CNS) pressor responses? The effect of potassium-loading on CNS pressor responses was studied in S rats on a low (0.3%) NaCl diet. Drinking a 2% KCl solution reduced the CNS pressor responses in S rats to both AII and hypertonic saline by 44% (p less than 0.025) and brought them down almost as low as in R rats. KCl added to the low NaCl dry diet also decreased the CNS pressor responses in S rats to AII and to hypertonic saline by 39% (p less than 0.01) and 59% (p less than 0.02) respectively. K-citrate added to the low NaCl diet was generally as effective as KCl in reducing CNS pressor responses. K-citrate reduced the angiotensin pressor response by 44% (p less than 0.001) and the hypertonic saline pressor response by 46% (p less than 0.05). Thus, potassium feeding greatly diminished the hyperactive CNS pressor responses in S rats. This CNS action may well explain a good part of the protective effect of KCl against NaCl hypertension in S rats.
Abnormal baroreflex control of heart rate in prehypertensive and hypertensive Dahl genetically salt-sensitive rats.
Authors: Gordon F J , Matsuguchi H , Mark A L
Published: September 2013

This study tested the hypothesis that in the Dahl model of genetic hypertension abnormal baroreflex function may precede and contribute to the development of hypertension. Sensitivity of baroreflex control of heart rate was assessed in conscious sensitive (S) and resistant (R) Dahl rats fed a high or low salt diet. Sensitivity of baroreflex control of heart rate was lower in S rats fed low salt although arterial pressure was not different from that of R rats. Hypertensive S rats showed resetting of baroreflexes to the higher pressure level without any further change in sensitivity. Pressor responses to phenylephrine were augmented in both prehypertensive and hypertensive S rats compared to R rats. Ganglionic blockade abolished this difference. In hypertensive S rats, ganglionic blockade decreased arterial pressure to levels not different than similarly treated R rats, indicating that neurogenic mechanisms contribute importantly to the early stages of hypertension in the Dahl model. These studies have identified impaired baroreflex function in prehypertensive and hypertensive Dahl S rats. This defect augments responses to pressor stimuli and may contribute to the development of salt-induced hypertension in the Dahl strain.
Opiate analogs, substance P, and baroreceptor reflexes in the rabbit.
Authors: Petty M A , Reid J L
Published: September 2013

The putative transmitters, enkephalins and substance P, and their binding sites have been identified in the nucleus of the solitary tract. Their role in the modulation of baroreceptor reflex activity is the subject of this study in the rabbit. A stable decarboxy analog of leu-enkephalin, RX 783016, which has mu receptor specificity, was used to attenuate the baroreflex sensitivity to intravenous phenylephrine. RX 783016, 50 micrograms/kg intracisternally, did not alter resting heart rate of blood pressure. Intravenous administration of the opiate receptor antagonist, naloxone, prevented the effects of RX 783016. Naloxone given alone significantly increased reflex sensitivity. Substance P given intracisternally in low doses (1 to 10 ng/kg) caused a dose-dependent pressor response, which was reduced by pretreatment with morphine and enhanced by naloxone. Bilateral sinoaortic denervation also enhanced the pressor response to substance P, but after deafferentation, naloxone had no further effect. It is proposed that enkephalin-containing neurons, acting through mu receptors, and substance P neurons influence baroreceptor reflex activity by modulating respectively the primary and second order neurons of the baroreceptor reflex.
The glomerular filtration barrier in the spontaneously hypertensive rat.
Authors: Evan A P , Luft F C , Gattone V , Connors B A , MaCarron D A , Willis L R
Published: September 2013

To determine whether the differences in the physiological characteristics of SHR and WKY kidneys might be related to differences in renal structure, we studied the kidneys of SHR and WKY rats utilizing scanning and transmission electron microscopy and latex perfusion of the glomerular vasculature. Scanning and transmission electron microscopy revealed a smaller diameter in the glomerular endothelial fenestrae of SHR compared to that in WKY rats even prior to the development of differences in blood pressure. With age, the density and diameter of SHR endothelial fenestrae progressively decreased, which was not true in WKY rats. Latex casts of glomerular vasculature showed the frequent presence of afferent arteriolar constriction in 12-week-old SHR. Thus, the filtration barrier of the SHR is abnormal. THe pathogenesis of hypertension in the SHR is complex and probably multifactorial; however, renal structural changes may contribute to the development and maintenance of hypertension. The afferent arteriolar constrictions may be the structural basis for the increased vascular resistance described in the SHR.
Aortic responses to vanadate: independence from (Na,K)-ATPase and comparison of Dahl salt-sensitive and salt-resistant rats.
Authors: Rapp J P
Published: September 2013

Vanadate at doses from 10(-4.5) to 10(-3) M caused a dose-dependent contraction of the rat aorta in vitro. Aortas of Dahl salt-hypertension sensitive (S) rats responded to vanadate with a greater contraction than Dahl salt-hypertension resistant (R) rats. In contrast, S and R aortic responses to depolarization with potassium were equal, and responses to norepinephrine were less in S than R. The mechanism by which vanadate causes the aortic response was studied in S rats. In aortic smooth muscle sodium-loaded by exposure to low potassium media followed by a norepinephrine-induced contraction, a relaxation induced with 5 mM potassium was not influenced by 10(-3) M vanadate. Since this potassium-induced relaxation is known to be a reflection of (NaK)-ATPase activity, these data show that vanadate (up to 10(-3) M does not inhibit (Na,K)-ATPase in intact smooth muscle cells although it is a known potent inhibitor of (Na,K)-ATPase in isolated cell membrane preparations. Response to vanadate was not changed by alpha-blockade with phentolamine or by blocking (Na,K)-ATPase with ouabain. Vanadate contraction was blocked by 4,4'-diisothiocyano-2,2'-disulfonic acid stilbene, a known inhibitor of anion transport, suggesting that vanadate anions must enter smooth muscle cells to induce contraction.
Abnormal erythrocyte cation transport in primary hypertension. Clinical and experimental studies.
Authors: De Mendonca M , Garay R P , Ben-Ishay D , Meyer P
Published: September 2013

Several abnormalities concerning sodium (Na+) transport in erythrocytes of essential hypertensive patients have been recently observed. An abnormal extrusion of an erythrocyte Na+ load was described in our laboratory. This defect appeared to be specific for essential hypertension since it was absent in the secondary forms of the disease. The present investigation was performed on 194 Caucasian subjects with essential hypertension or born of hypertensive parents, 86 normotensive controls, and 14 families (78 subjects) studied over two to three generations. The distribution pattern of the erythrocyte defect is compatible with the expression of a single gene transmitted according to an autosomic and dominant mode. To confirm the genetic association between the red blood cell abnormality and primary hypertension, genetically hypertensive rats were investigated in parallel to our clinical studies. A reduction in the net Na+ extrusion from red blood cells was found in two varieties of genetic hypertension (SHR and H-prone-Na+-sensitive Sabra rats). The abnormality could be detected before the development of a significant hypertension. When these various rat sub-strains were acutely or chronically loaded with Na+ (either intraperitoneally or orally), a significant increase in erythrocyte Na+ content was observed only in those substrains having a genetic propensity to develop hypertension. This finding, which appears to be a consequence of the reduction in net Na+ efflux, is of interest for several reasons. It confirms the existence of a close association between a genetic predisposition to develop high blood pressure and cell Na+ retention in the presence of an excess Na+ intake. It draws attention to the possible role of intracellular Na+ in the pathogenesis of primary hypertension. Of more practical importance, the abnormal Na+ handling in erythrocytes may be a genetic marker of primary hypertension.
Mechanism of acid-activation of renin: role of kallikrein in renin activation.
Authors: Hsueh W A , Carlson E J , Israel-Hagman M
Published: September 2013

Dialysis of plasma in pH 3.3 and then pH 7.5 is a method commonly used to activate plasma inactive renin. Endogenous plasma kallikrein has been shown to participate in activation during neutral dialysis. The present studies demonstrate that plasma inactive renin is fully activated following dialysis to pH 3.3 at 10 degrees C. Activation by low pH is a reversible process when followed by titration to a pH greater than 4.0. The rate of reversal of acid activation increases with increasing pH and temperature, reaching a maximum at pH 7.0 ad 37 degrees C. the disappearance of activated renin is not due to its destruction, because dialysis back to pH 3.3 fully restores activation. A preparation of renin zymogen devoid of active renin also shows complete reversal of activation. The Km of acid-activated renin is the same as that of endogenous active renin. Acid-activated renin (untreated by protease) elutes with an apparently greater Stokes radius than non-acid-treated inactive renin on Sephadex G-100. Once reversal of acid activation occurs, renal or plasma kallikrein has no effect on renin. However, once kallikrein acts on acid-activated renin, activation is no longer reversible. These data can explain the mechanism of acid activation of renin and the contribution of plasma kallikrein to renin activation in vitro. At low pH, inactive renin appears to undergo a conformational change such that the active site is accessible. Acid may unfold the renin molecule, as suggested by an increase in Stokes radius following acid dialysis. Kallikrein may then cleave a small peptide that permanently maintains acid-activated renin in an active state. Thus, renin zymogen must be in an active conformation such as that induced by acid to be "acted upon" by kallikrein, suggesting that other factors, in addition to renal kallikrein, may be involved in renin activation in vivo.
Anxiety, anger, and neurogenic tone at rest and in stress in patients with primary hypertension.
Authors: Sullivan P , Schoentgen S , DeQuattro V , Procci W , Levine D , Van der Meulen J , Bornheimer J
Published: September 2013

To determine whether basal blood pressure or pressor responses to stress are related to sympathetic nerve tone or to psychological factors in hypertensives, 15 hypertensives and 13 normotensives were studied by mean of a self-administered questionnaire, isometric handgrip exercise (IHE), and the mental stress of serial subtraction. Plasma norepinephrine (NE), epinephrine (E), blood pressure (BP) and heart rate (HR) were measured before and at the end of IHE and mental stress. A greater number of hypertensives had suppressed anger (p less than 0.01) and scored higher on anxiety trait (p less than 0.01) and depression (p less than 0.05). Prestress (IHE and mental) BP and NE values were significantly greater in hypertensives (all p less than 0.01). During IHE, both groups had a significant increase of BP, HR, and NE (all p less than 0.01) but E rose in hypertensives only (p less than 0.05). The percentage change of BP, HR, NE, and E during IHE was similar in both groups. The changes of BP and HR were not related to NE or E. During mental stress, HR (p less than 0.01) and E (p less than 0.05) increased in both groups. However, BP (systolic and diastolic) increased in normotensives only (p less than 0.01). Plasma NE contents were unchanged in both groups. There were significant positive correlations of anxiety trait with systolic BP (p less than 0.05), diastolic BP (p less than 0.05), and NE (p less than 0.05) and E (p less than 0.05). Although hypertensives had increased neurogenic tone related perhaps to inward anger and anxiety, the percentage responses of neurogenic tone and BP to IHE were equivalent to those of normotensives. The challenge of serial subtraction did not elicit further noradrenergic or pressor responses in hypertensives. Suppressed anger and anxiety, via increased basal neurogenic tone, may be pathogenic factors in some patients with primary hypertension.
Effect of salt loading on the cardiovascular response to stress in adolescents.
Authors: Falkner B , Onesti G , Angelakos E
Published: September 2013

This study investigated, in normotensive adolescents, three accepted risk factors for essential hypertension (EH): stress, dietary salt, and parental history (genetic risk). The cardiovascular response to mental stress was evaluated before and after salt loading in eight subjects without, and in seven with, a family history (FH) of EH. The effect of salt loading on the FH positive group was to increase significantly the stress-induced systolic and diastolic pressure while the heart rate response decreased. Salt loading resulted in no change in cardiovascular response to stress in the FH negative group.
Antihypertensive effect of transplant of rat kidney or its unclipping. Hemodynamic effects and control mechanisms.
Authors: Hoobler S W , Eto T , Welk R , Burge H
Published: September 2013

The acute transplantation of a normal kidney into a recipient rat with Goldblatt one-kidney, one clip hypertension (1K1C) results in a blood pressure (BP) fall toward but not below normal levels within 1 hour. Removal of the clip in a 1K1C hypertensive rat also normalizes the BP rapidly. These changes are not mediated by external fluid loss and occur after indomethacin pretreatment, but are associated with a fall in cardiac output. The mechanism of release of a depressor secretion from the kidney transplant appears to be under barostatic control. Thus, transplanting a kidney into a hypertensive recipient caused a prompt BP decline, whereas transplanting an SHR kidney into a hypertensive recipient did not lower the BP. The prompt BP fall seen after unclipping also indicates that abrupt exposure of the kidney to a high perfusion pressure initiates the release of some depressor agent. When the recipient rat was made hypertensive by injecting renin, the kidney transplant did not lower the BP. When angiotensin in subpressor dose was infused into the renal artery of the kidney transplant, the BP of the recipient did not fall, whereas infusion of norepinephrine in equiconstrictor doses did not prevent the depressor response. These experiments suggest that, in addition to a barostatic stimulus for depressor release, angiotensin acts as a specific inhibitor.
Long-term converting enzyme inhibition and sympathetic nerve function in hypertensive humans.
Authors: Zanella M T , Bravo E L , Fouad F M , Tarazi R C
Published: September 2013

Orthostatic hypotension is uncommon during oral converting enzyme inhibition, even when combined with salt depletion. To assess the mechanisms responsible for the cardiovascular homeostasis in this condition, we studied the blood pressure (BP), heart rate (HR), total plasma catecholamines (CA), and plasma renin activity (PRA) responses after 20 minutes of 60 degrees head-up tilt in four groups of hypertensive patients. Group 1 included seven untreated patients; Group 2, eight patients on converting enzyme inhibitor (captopril) therapy; Group 3, six patients on diuretic therapy and Group 4, 15 patients on combined captopril and diuretic therapy. Long-term converting enzyme inhibition alone or in combination with diuretics resulted in reduction of mean arterial pressure (MAP) associated with a marked increase in PRA and fall in plasma aldosterone concentration (PAC). Pronounced increases in HR and plasma CA on tilt were observed in all groups. In Groups 1, 2, and 3, BP was maintained during tilt; in Group 4, three patients fainted between 5 and 15 minutes while the other 12 had a normal response to tilt. Plasma catecholamines increased more significantly after 15 and 20 minutes of tilt, more in Groups 3 and 4 than in Group 1, while no differences in HR response were observed among groups. Results suggest that sympathetic compensatory mechanisms are adequate in the majority of patients to maintain BP during converting enzyme inhibition even when combined with salt depletion. In a few who exhibited orthostatic hypotension, a vasovagal attack seemed to be responsible for bradycardia and fall in BP.
Blood pressure and prolactin: effects of guanfacine. Three-year follow-up study.
Authors: Hauger-Klevene J H , Pinkas M B , Gerber S
Published: September 2013

Serum prolactin was measured in 76 patients with essential hypertension: 47.4% had elevated serum prolactin, and those with organ damage had presented higher prolactin than those with Phase I (WHO) hypertension. The effect of prolonged treatment (3 years) with guanfacine, an alpha-adrenoceptor stimulant drug, on blood pressure levels, heart rate, and prolactin was evaluated in 15 patients with moderate essential hypertension (WHO: Phase II) and hyperprolactinemia. Treatment produced a marked reduction in blood pressure levels and heart rate. Guanfacine decreased serum prolactin significantly (p less than 0.001), and the inhibition persisted during the 3-year follow-up. The daily dosage of guanfacine did not have to be changed during the 3 years of treatment. Side effects of guanfacine were only observed during the first 3-4 months of therapy. The hypotensive effect of guanfacine was increased by the administration of a diuretic, a vasodilator, or a beta-adrenergic blocking drug. The results indicate that guanfacine administered alone or in combination is an effective drug for treatment of patients with essential hypertension. The inhibitory effect of guanfacine on prolactin suggests that hypothalamic or extrahypothalamic adrenergic pathways may participate in the regulation of prolactin secretion.
Profile of hypertensives as a determinant of long-term antihypertensive medication needs.
Authors: Madhavan S , Davis T , Alderman M H
Published: September 2013

The experience of 110 hypertensives who participated in a worksite stepped-care treatment program has been examined to draw a patient profile at entry that would determine medication needs on a long-term basis. Patients entered untreated with a blood pressure (BP) level of greater than or equal to 160 mm Hg systolic and/or greater than or equal to 95 mm HG diastolic (DBP) and had a minimum follow-up of 1 year. Treatment was initiated with diuretics, and additional drugs were added as necessary to achieve BP control. Patients were divided into three groups according to initial DBP levels: Group A (33 patients, greater than or equal to 105 mm Hg), Group B (43 patients, 95-104 mm Hg), and Group C (34 patients, less than 95 mm Hg). Using a life table method, we analyzed the therapeutic experience of these patients to obtain 5-year cumulative rates of adding a second drug to diuretics. Within the first 2 years of treatment, the cumulative rates were: 64% in Group A, 33% in Group B, and 23% in Group C. In all three groups the rates after the second year remained stable. This stepped-care approach resulted in BP control (less than 160/95) which ranged from 78% in the first year to 96% in the fifth year. Findings suggest that initial DBP level and age are principal factors in determining medication needs. Furthermore, at higher DBP levels, younger nonwhite and younger white males are most likely to require a second drug within the first year of treatment. The need for a second drug is apparent within the first 2 years.
Four-year experience in a hypertension control program. Operation aspects.
Authors: Espinosa de Restrepo H
Published: September 2013

Four-year experience with a hypertension control program in Medellín, Colombia, is reported. A simple and reproducible model is presented to be given mainly by general practitioners with follow-up care delegated to well-trained practical nurses. The model has proved efficient in avoiding dropouts and obtaining lower blood pressure readings. Survival and compliance curves indicate that both are affected for the whole length of the follow-up period. In particular, periodical evaluation allows better compliance rates. Paramedical personnel participation and educational activities are the most important strategies for improving compliance.
Rat (Ile5) but not bovine (Val5) angiotensin raises plasma norepinephrine in rats.
Authors: Speth R C , Khosla M C , Spech M M , Ferrario C M
Published: September 2013

A part of the vasoconstrictor activity of angiotensin II (AII) may result from its ability to enhance norepinephrine (NE) release from sympathetic noradrenergic nerve terminals. To investigate this proposed pressor mechanism of AII, the effects of intravenous (i.v.) infusion of AII on blood pressure and plasma catecholamines in pithed rats were determined. Two naturally occurring angiotensins, valine5 AII (bovine) and isoleucine5 AII (rat), were administered in equal (72 ng/min) doses. Valine5 AII caused an 80% increase in mean arterial pressure (MAP) from 54 +/- 4 to 97 +/- 19 mm Hg. Isoleucine5 AII caused an 82% increase in MAP from 49 +/- 5 to 89 +/- 18 mm Hg. Neither angiotensin caused a change in heart rate, suggesting that pithing completely destroyed the central baroreceptor reflex mechanism. Plasma catecholamines were differentially affected by the peptides:isoleucine5 AII significantly increased plasma NE concentration by 82% compared to saline-infused rats (p less than 0.01). Valine5 AII did not significantly affect plasma NE concentration. Plasma dopamine and epinephrine concentrations were not significantly altered by infusion of either analog. Despite the significant increases in plasma NE concentrations with isoleucine5 in AII-infusion rats, there was no correlation between plateau MAP or the percent increase in MAP and plasma NE concentrations of individual animals within this group. The ability of angiotensin to elevate MAP, increase NE release from sympathetic nerve terminals, as well as potential differences in the actions of angiotensins in different species, and angiotensin receptor heterogeneity, are discussed.