Transient Increase In Blood Pressure Research Articles

Does Cigarette Use Modify Blood Pressure Measurement or the Effectiveness of Blood Pressure Medications?

Smoking is the most common cause of avoidable cardiovascular disease worldwide. The incidence of hypertension is increased in people who smoke 15 or more cigarettes per day. The acute and chronic effects of cigarette smoking are worth reviewing, as this may impact the choice of drugs and dosing considerations in the hypertensive population. The acute effects of smoking on blood pressure (BP) are related to overactivity in the sympathetic nervous system, which results in an increase in myocardial oxygen consumption due to an acute increase in BP, heart rate, and myocardial contractility. Acutely, BP rises transiently within minutes and starts to decrease back to baseline by 15 minutes after smoking a cigarette. This transient increase in BP may be most prominent after the first cigarette of the day even in habitual smokers. One study showed an average 20-mm Hg increase in systolic BP after the first cigarette. This effect may be amplified with caffeine use. 5 Interestingly, habitual smokers have been shown in some studies to have lower BP than nonsmokers, and this appears to be related to decreased body weight. A major contributor to the lower BP is likely from cotinine, the major metabolite of nicotine, which has some vasodilatory effects. Despite this observation, smoking should be avoided in any hypertensive patient because it can markedly increase the risk of cardiovascular disease and result in the progression of chronic kidney disease. Chronic smoking also induces arterial stiffness, which can persist for a decade after smoking cessation, and this alone is an increased cardiovascular risk factor. Smoking has also been shown to cause a decrease in left ventricular function in asymptomatic individuals. A recent prospective study examined factors associated with renal function decline in 53 hypertensive patients whose serum creatinine increased from 1.5 mg ⁄dL to 1.9 mg ⁄dL despite a significant decrease in mean arterial pressure (127–97 mm Hg). Smoking was the most significant independent factor underlying the progression of chronic kidney disease in smokers vs nonsmokers. The mechanism is unclear but may be due to an acute increase in systemic hypertension from smoking resulting in glomerular hypertension. Cigarette smoking can also affect metabolism of antihypertensive drugs and their efficacy. b-Blockers in particular have been implicated in being less efficacious when taken by smokers. b-Blockers have been shown to be less effective for BP and heart rate reductions in smokers compared with nonFrom the Department of Medicine, Hypertension Program, University of Pennsylvania School of Medicine, Philadelphia, PA Address for correspondence: Debbie L. Cohen, MD, Renal Division, University of Pennsylvania School of Medicine, 210 White Building, Philadelphia, PA 19104 E-mail: cohendl@mail.med.upenn.edu

Phase II study of NGR-hTNF, a selective vascular targeting agent (VTA), administered as single agent in patients (pts) with colorectal cancer (CRC) refractory to standard regimens

4088 Background: NGR-hTNF is a VTA exploiting a tumor-homing peptide (NGR) that selectively binds to an aminopeptidase N/CD13 overexpressed by tumor blood vessels. In preclinical models, NGR-hTNF showed antitumor activity both at low and at high doses. Methods: Pts with CRC resistant/refractory to standard treatments, including biological agents, were treated with low-dose NGR-hTNF given intravenously at 0.8 μg/m2 as 1-hour infusion every 3 weeks (q3w). This phase II trial had a 2-stage design with 16 and 27 pts to be enrolled after first and second stage, respectively. Progression-free survival (PFS) was the primary end-point with reassessment performed q6w. Results: From January to May 2007, 33 pts with radiologically- documented progressive disease after last therapy were evaluated over 111 cycles (range, 1–10). Pts characteristics were: median age: 65 years (range, 53 to 79); M/F 16/17; PS 0/1 26/7. Median number of prior regimens was 3 (range, 2 to 5). Eight pts (25%) were pre-treated with ≥4 lines and 22 (67%) with biological agents. Neither grade 3–4 treatment-related adverse events nor toxicity-related deaths were observed. Main grade 1–2 toxicities per patient were infusion-related chills (47%) and transient blood pressure increase (9%). One partial response (3%) lasting 5 months and 12 stable diseases (36%) were reported. Median PFS was 2.5 months (95% CI, 2.2–2.8). In a post-hoc analysis, no differences in PFS were detected according to baseline characteristics. With a median follow-up time of 18.4 months (95% CI, 18.3–18.5), 11 pts (33%) were still alive. Median overall survival (OS) was 13.1 months and the 2-year OS rate was 22%. In the subset of stable or responder pts, the median PFS and OS were 3.8 months and 15.4 months, respectively. The 6-month PFS rate in the prior-biological and biological-naïve cohorts was 5% and 20%, respectively, whereas 1-year OS rate was 41% and 72%, respectively. Conclusions: Based on the favorable toxicity profile and disease control in heavily pre-treated CRC patients, NGR-hTNF will be further developed in combination with standard chemotherapy. [Table: see text]

The underwater environment: cardiopulmonary, thermal, and energetic demands

Water covers over 75% of the earth, has a wide variety of depths and temperatures, and holds a great deal of the earth's resources. The challenges of the underwater environment are underappreciated and more short term compared with those of space travel. Immersion in water alters the cardio-endocrine-renal axis as there is an immediate translocation of blood to the heart and a slower autotransfusion of fluid from the cells to the vascular compartment. Both of these changes result in an increase in stroke volume and cardiac output. The stretch of the atrium and transient increase in blood pressure cause both endocrine and autonomic changes, which in the short term return plasma volume to control levels and decrease total peripheral resistance and thus regulate blood pressure. The reduced sympathetic nerve activity has effects on arteriolar resistance, resulting in hyperperfusion of some tissues, which for specific tissues is time dependent. The increased central blood volume results in increased pulmonary artery pressure and a decline in vital capacity. The effect of increased hydrostatic pressure due to the depth of submersion does not affect stroke volume; however, a bradycardia results in decreased cardiac output, which is further reduced during breath holding. Hydrostatic compression, however, leads to elastic loading of the chest wall and negative pressure breathing. The depth-dependent increased work of breathing leads to augmented respiratory muscle blood flow. The blood flow is increased to all lung zones with some improvement in the ventilation-perfusion relationship. The cardiac-renal responses are time dependent; however, the increased stroke volume and cardiac output are, during head-out immersion, sustained for at least hours. Changes in water temperature do not affect resting cardiac output; however, maximal cardiac output is reduced, as is peripheral blood flow, which results in reduced maximal exercise performance. In the cold, maximal cardiac output is reduced and skin and muscle are vasoconstricted, resulting in a further reduction in exercise capacity.

Lysophosphatidic Acid Receptors 1 and 2 Play Roles in Regulation of Vascular Injury Responses but Not Blood Pressure

Phenotypic modulation of vascular smooth muscle cells (SMCs) is essential for the development of intimal hyperplasia. Lysophosphatidic acid (LPA) is a serum component that can promote phenotypic modulation of cultured SMCs, but an endogenous role for this bioactive lipid as a regulator of SMC function in vivo has not been established. Ligation injury of the carotid artery in mice increased levels in the vessel of both autotaxin, the lysophospholipase D enzyme responsible for generation of extracellular LPA, and 2 LPA responsive G protein-coupled receptors 1 (LPA1) and 2 (LPA2). LPA1(-/-)2(-/-) mice were partially protected from the development of injury-induced neointimal hyperplasia, whereas LPA1(-/-) mice developed larger neointimal lesions after injury. Growth in serum, LPA-induced extracellular signal-regulated protein kinase activation, and migration to LPA and serum were all attenuated in SMCs isolated from LPA1(-/-)2(-/-) mice. In contrast, LPA1(-/-) SMCs exhibited enhanced migration resulting from an upregulation of LPA3. However, despite their involvement in intimal hyperplasia, neither LPA1 nor LPA2 was required for dedifferentiation of SMCs following vascular injury or dedifferentiation of isolated SMCs in response to LPA or serum in vitro. Similarly, neither LPA1 nor LPA2 was required for LPA to elicit a transient increase in blood pressure following intravenous administration of LPA to mice. These results identify a role for LPA1 and LPA2 in regulating SMC migratory responses in the context of vascular injury but suggest that additional LPA receptor subtypes are required for other LPA-mediated effects in the vasculature.

A phase II study of NGR-hTNF, a novel vascular targeting agent (VTA), administered as single agent at low dose in pretreated patients (pts) with advanced hepatocellular carcinoma (HCC)

15544 Background: NGR-hTNF is a VTA exploiting a tumor-homing peptide (NGR) that selectively binds to aminopeptidase N/CD13 highly expressed on tumour blood vessels. NGR-hTNF combines activity on tumour vascular permeability and direct anticancer activity. In preclinical models, NGR-hTNF showed antitumor activity either at low doses or at high doses. Methods: Pts with unresectable or metastatic HCC were treated with a low dose of NGR-hTNF given at 0.8 mcg/m2 as 1-hour intravenous infusion every 3 weeks (q3w). This phase II trial had a 2-stage design with 16 and 27 pts to be enrolled in stage 1 and 2, respectively. Progression-free survival (PFS) was the primary end point and tumor reassessment (WHO criteria) was performed q6w. Results: 16 pts with progressive disease following prior loco-regional treatment (63%), systemic therapy (50%), or both (19%), were recruited into the first stage. Pts characteristics were: M/F 13/3; median age 66 years (range, 53 to 79); PS 0/1 11/5; Child-Pugh score A/B: 14/2. To date, 46 cycles (median 2, range: 1–8) have been administered and 5 pts (28%) received ≥4 doses. In the first step of the trial, 5 out of 14 assessable pts (36%) had a stabilization of disease (SD) with a median duration of 4.3 months (range: 2.7–6.2). The median PFS was 2.4 months (95% CI: 1.5–3.1). Neither grade 3–4 treatment-related adverse events nor toxicity-related death were observed. Main grade 1–2 toxicities per patient were infusion-related constitutional symptoms, including chills (59%), and transient blood pressure increase (6%). The study is currently recruiting patients into the second stage and in a subsequent cohort of 12 patients treated with a weekly schedule of administration. Conclusions: NGR-hTNF given at 0.8 mcg/m2 q3w is well tolerated and appears to induce promising disease control in pretreated patients with advanced HCC. The drug will be further explored as single agent. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration MolMed

Kidney in Hypertension

Regulation of blood pressure is a complex integrated response involving a variety of organ systems including the central nervous system (CNS), cardiovascular system, kidneys, and adrenal glands. These systems modulate cardiac output, fluid volumes, and peripheral vascular resistance, the key determinants of blood pressure. More than 40 years ago, Guyton and Coleman1 developed computer models of arterial pressure control, attempting to incorporate the known variables impacting blood pressure homeostasis. The conclusion of this analysis was that regulation of sodium excretion by the kidney and consequent effects on body fluid volumes made up the critical pathway determining the chronic level of intra-arterial pressure. Our own studies of the physiology of blood pressure regulation have focused on the renin-angiotensin (Ang) system (RAS) using genetically modified mouse models. Highly conserved through phylogeny, the RAS is an essential regulator of blood pressure and fluid balance. This biological system is a multienzymatic cascade in which angiotensinogen, its major substrate, is processed in a 2-step reaction by renin and Ang-converting enzyme (ACE), resulting in the sequential generation of Ang I and Ang II. Along with its importance in maintaining normal circulatory homeostasis, abnormal activation of the RAS can contribute to the development of hypertension and target organ damage. The importance of the RAS in clinical medicine is highlighted by the impressive efficacy of pharmacological agents that inhibit the synthesis or activity of Ang II.2–5 At the cellular level, responsiveness to Ang II is conferred by expression of Ang receptors. Ang receptors can be divided into 2 pharmacological classes: type 1 (AT1) and type 2, based on their differential affinities for various nonpeptide antagonists.6,7 Studies using these antagonists suggested that most of the classically recognized functions of the RAS are mediated by AT1 receptors. Gene targeting studies confirmed these conclusions.8 AT …

Suppression of detrusor overactivity in rats with bladder outlet obstruction by a type 4 phosphodiesterase inhibitor

To investigate the effects of a selective type 4 cyclic nucleotide phosphodiesterase (PDE4) inhibitor, IC486051, on bladder activity in normal rats and those with and bladder outlet obstruction (BOO), as inhibition of PDE4 leads to elevation of intracellular cAMP levels and relaxation of smooth muscle. BOO was induced in female Sprague-Dawley rats by tying a silk ligature around the urethra. At 4 or 6 weeks after inducing BOO, conscious rats were assessed by cystometry with the urethral ligature intact. In unobstructed rats, blood pressure was also measured. In unobstructed rats, IC486051 (0.1 mg/kg intravenously) produced no significant changes in cystometric variables, while at a dose of 0.5 mg/kg maximum voiding pressure was reduced by 34%. At both doses, there was a small, transient increase in blood pressure. In both 4- and 6-week BOO rats IC486051 dose-dependently decreased the number and amplitude of non-voiding bladder contractions by up to 80%, relative to pre-treatment values. At doses of 0.1 and 0.5 mg/kg IC486051 had no significant effect on voiding variables. In the 4-week BOO rats, a dose of 1.0 mg/kg decreased bladder capacity, voided volume and residual volume by 21%, 32% and 18%, respectively. In 6-week BOO rats, a dose of 1.0 mg/kg decreased maximal voiding pressure by 17% and pressure threshold for voiding by 28%. In both groups of rats with BOO, voiding efficiency was unchanged. A selective PDE4 inhibitor can effectively suppress detrusor overactivity in rats with BOO, at doses that have no effect on voiding bladder contractions. Thus, selective PDE4 inhibitors should be considered for the treatment of overactive bladder in patients with BOO.

Are Transient Increases in Blood Pressure During the Treadmill Stress Test Associated With Headache?

We aimed to investigate whether transient increases in blood pressure (BP) are associated with headache, by provoking hypertension in 50 non-hypertensive cephalalgia sufferers (Ce), 50 hypertensive cephalalgia sufferers (HyCe) and 50 healthy subjects (C) with a treadmill stress test. Occurrence of headache among groups did not differ (P = 0.81); however, women developed headache more frequently than men (P < 0.0001). The 35 individuals who developed headache during the test compared with those who did not (regardless of their original group) had higher absolute diastolic BP and higher absolute and relative diastolic BP increase during the test (P < 0.0001). HyCe patients that developed headache had higher diastolic BP than those that did not (P < 0.002). For each group, the absolute/relative mean increases of systolic/diastolic BP did not differ between patients that developed headache and those that did not excepting relative diastolic BP increase in Ce (28% vs. 15%, P = 0.006). The appearance of headache during dynamic exercise is not associated with a history of headache or hypertension. In non-hypertensive cephalalgia sufferers, relative diastolic BP increases of >27% are associated with headache attacks whereas in HyCe sufferers absolute diastolic BP values may be more important.

The Treatment Should Not Be Worse Than the Disease

Dr. Beilin does not consider the use of phenylephrine infusions to be justified given the “minor” consequences of hypotension during spinal anesthesia for cesarean delivery. We disagree. One should not underestimate the importance of hypotension and its prevention. Dr. Beilin contends that serious adverse effects from hypotension are “almost nonexistent.” However, history warns us that major complications can indeed occur when hypotension is inadequately managed.1Dr. Beilin cited several articles2–4to support his contention, but careful reading of these reveals somewhat different messages. Macarthur2reported that “several reviews of maternal anesthetic deaths identified inadequately treated maternal hypotension as the major source of spinal anesthesia's morbidity and mortality.” Desalu and Kushimo3attributed low Apgar scores in some neonates in their study to relatively long durations of hypotension and stated that hypotension should be avoided in pregnant patients. Juhani and Hannele4emphasized the high incidence of minor complications and recommended that “hypotensive periods should be prevented.” Surprisingly, Dr. Beilin suggests that hypotension is not associated with neonatal acidosis or low Apgar scores. Datta et al. 5showed just such an association more than 20 yr ago. More recently, concern has been expressed that spinal anesthesia depresses fetal pH and base excess.6We believe the most important cause of this is hypotension and the way that it is treated.7Dr. Beilin trivializes the seriousness of nausea and vomiting. Nausea and vomiting can cause significant distress to the patient and can interfere with surgery.8We regard its prevention as an important clinical indicator of quality of care. Examination of closed claims has emphasized the prominence of “minor” injuries including emotional distress in obstetric anesthesia cases,9and thus, there may also be medicolegal implications. Pulmonary aspiration has occurred;9that's pretty dangerous.Dr. Beilin describes treatment of hypotension as “straightforward.” The large volume of research dedicated to this subject argues otherwise. There remain major controversies over the choice, dose, timing, and methods of administration of vasopressors and fluids. Dr. Beilin implies that it is sufficient to wait for hypotension to occur and then treat it with small boluses of ephedrine. It was the inadequacy of this very approach that several years ago stimulated us to direct research toward finding a better way.10We make no excuses for our aggressive approach to the prevention of hypotension. Our work indicates that this provides the best outcomes for mother and baby.11Although, as stated in our article, we do advocate some caution with phenylephrine infusions because of the potential for blood pressure to transiently increase above baseline, we disagree that use of direct intraarterial blood pressure monitoring is necessary when using this technique in healthy patients. From our experience11–15of many years of using infusions of α agonists in many hundreds of patients, we have found measurement of noninvasive blood pressure every minute until delivery together with continuous monitoring of heart rate to be quite sufficient and, contrary to Dr. Beilin's opinion, quite practical. We have not found small transient increases in blood pressure and relative slowing of maternal heart rate to be harmful. Arguably, this is a safer physiologic state than profound vasodilation with marked tachycardia, the likely alternative. Furthermore, in clinical practice, with continuous heart rate monitoring and the freedom to titrate the phenylephrine infusion without the strict constraints of a study protocol, hypertension is less of a problem.No treatment is perfect. But make not the mistake of underestimating the disease.*The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong, China. warwick@cuhk.edu.hk

Medical Management of the Traumatic Consequences of Civil Unrest Incidents

Medical Management of the Traumatic Consequences of Civil Unrest Incidents

Nitric Oxide Scavenging by Hydroxocobalamin May Account for Its Hemodynamic Profile

Background. Antidotal doses of hydroxocobalamin are associated with transient increases in blood pressure in some animals and humans. These studies in anesthetized rabbits were undertaken to explore the possible mechanisms underlying the hemodynamic effects of hydroxocobalamin by investigating 1) possible hemodynamic effects of cyanocobalamin, which is formed on a molar-to-molar basis when hydroxocobalamin binds cyanide, and 2) the interference of hydroxocobalamin with the endothelial nitric oxide system. Methods. Study 1 investigated the hemodynamic effects of cyanocobalamin. This study included two treatment arms: 1) cyanocobalamin (75 mg/kg, IV) followed by saline (n = 7) and 2) saline followed by cyanocobalamin (n = 7). Study 2 assessed the hemodynamic effects of hydroxocobalamin (75 mg/kg, IV) in the presence and absence of the nitric oxide synthase inhibitor L-Nω-nitro-L-arginine methyl ester (L-NAME; 30 mg/kg, IV). Nitric oxide synthase inhibition itself increases blood pressure. Thus, as part of Study 2, the hemodynamic effects of hydroxocobalamin were also investigated in the presence of an equipressor dose of angiotensin II (ANGII; 0.05 μg/kg/min, IV) in order to determine whether elevated blood pressure per se could interfere with hydroxocobalamin's hemodynamic effects. This study included six treatment arms (designated as first treatment + second treatment): saline + saline (n = 5), L-NAME + saline (n = 7), saline + hydroxocobalamin (n = 7), L-NAME + hydroxocobalamin (n = 7), ANGII + hydroxocobalamin (n = 7), and ANGII + saline (n = 7). Results. In Study 1, the effects of cyanocobalamin on hemodynamic parameters were indistinguishable from those of saline. In Study 2, hydroxocobalamin infusion was associated with moderate hemodynamic effects, including an increase in systemic vascular resistance, an increase in blood pressure, and a decrease in cardiac output. Administration of L-NAME abolished the effects of hydroxocobalamin on all hemodynamic parameters. ANGII at a dose producing a pressor response comparable to that of L-NAME did not influence the hydroxocobalamin-associated hemodynamic changes. Conclusion. These studies in anesthetized rabbits demonstrate that the moderate pressor effect of hydroxocobalamin is not related to the formation of cyanocobalamin but is very likely related to the scavenging of nitric oxide by hydroxocobalamin.

Blood Pressure Responses of Endothelin-11-31 Within the Rostral Ventrolateral Medulla Through Conversion to Endothelin-11-21

Endothelin-1 1-31 (ET-1 1-31), a novel member of the endothelin family comprising 31 amino acids and derived from the selective hydrolysis of big ET-1 by chymase, directly activates endothelin receptors or converts to ET-1 1-21 by ET converting enzyme (ECE). The cardiovascular effects of central ET-1 1-31 are not identified. The present study was designed to investigate the cardiovascular actions of ET-1 1-31 within the rostral ventrolateral medulla (RVLM) in anesthetized rats. Bilateral injection of ET-1 1-31 (0.5, 1, and 2 pmol for each side) into the rostral ventrolateral medulla produced an initial pressor and/or a long-lasting hypotensive action but did not affect HR. Unilateral microinjection of 2 and 4 pmol of ET-1 1-31 into the rostral ventrolateral medulla only produced a significant (P < 0.05) transient increase in blood pressure by an average of 13 and 12 mm Hg, respectively, whereas unilateral microinjection of 8 pmol of ET-1 1-31 produced a sustained fall in blood pressure (from 92 +/- 6 to 69 +/- 8 mm Hg, P < 0.05). The transient pressor effect of unilaterally injecting ET-1 1-31 (4 pmol) into the rostral ventrolateral medulla was completely abolished by pretreatment with either ETA receptor antagonist BQ123 (83 +/- 2 versus 84 +/- 5 mm Hg, P > 0.05) or ET converting enzyme inhibitor phosphoramidon (99 +/- 5 versus 99 +/- 7 mm Hg, P > 0.05) but not ETB receptor antagonist IRL1038 (89 +/- 6 versus 96 +/- 7 mm Hg, P < 0.05). In addition, prior injection of phosphoramidon also completely abolished the long-lasting hypotension of intra-RVLM ET-1 1-31 (8 pmol) but did not modify the depressor action of intra-RVLM ET-1 1-21 (from 100 +/- 6 to 76 +/- 8 mm Hg, P < 0.05). In conclusion, the current results suggest that the cardiovascular effects of intra-RVLM ET-1 1-31 might be the result of conversion of ET-1 1-31 to ET-1 1-21 through activation of ETA receptors.

Adenosine as a mediator of macula densa-dependent inhibition of renin secretion

Adenosine acting through A(1) adenosine receptors (A1AR) has been shown previously to be required for the vasoconstriction elicited by high luminal NaCl concentrations at the macula densa (MD). The present experiments were performed to investigate a possible role of A1AR in MD control of renin secretion in conscious wild-type (WT) and A1AR-deficient mice. The intravenous injection of NaCl (5% body wt) reduced plasma renin concentration (PRC; ng ANG I x ml(-1) x h(-1)) from 1,479 +/- 129 to 711 +/- 77 (P < 0.0001; n = 18) in WT mice but did not significantly change PRC in A1AR-/- mice (1,352 +/- 168 during control vs. 1,744 +/- 294 following NaCl; P = 0.19; n = 17). NaCl injections also caused a significant reduction in PRC in beta(1)/beta(2)-adrenergic receptor-/- mice (298 +/- 47 vs. 183 +/- 42; P = 0.03; n = 6). Injections of isotonic NaHCO(3) (5% body wt) elicited significant increases in PRC in both WT and A1AR-/- mice. NaCl as well as NaHCO(3) injections were accompanied by transient increases in blood pressure, heart rate, and activity that were similar in WT and A1AR-/- mice. The increase in PRC caused by an intraperitoneal injection of furosemide (40 mg/kg) was comparable in WT and A1AR-/- mice, and it was accompanied by similar transient increases in blood pressure, heart rate, and activity. Similarly, the stimulation of PRC caused by hydralazine was the same in WT and A1AR-/- mice. We conclude that the inhibition of renin secretion in response to an increase in NaCl at the MD requires A1AR and therefore appears to be adenosine dependent, whereas the stimulation of renin secretion during reductions in MD NaCl transport or arterial pressure does not require functional A1AR.

Transient increases in blood pressure affect sensory-motor activation following stroke using functional MR imaging in the rat

Transient increases in blood pressure affect sensory-motor activation following stroke using functional MR imaging in the rat

Evaluating the safety and tolerability profile of acute treatments for migraine

Among the medications that have been used as acute treatments for migraine are nonspecific agents, including nonsteroidal anti-inflammatory drugs (NSAIDs), analgesics (either single or combination), and narcotics, as well as migraine-specific medications, including ergot alkaloids and triptans (5-hydroxytryptamine 1B/1D agonists). All of these drugs have side effects that vary in type and severity. Side effects of nonspecific medications, including gastrointestinal (GI) and renal effects with NSAIDs and cognitive effects and the potential for abuse with narcotics and butalbital-containing medications, have been documented over time, as these medications have been used for various indications. Side effects of the migraine-specific medications include GI and vascular symptoms with the ergots; for the triptans, they include chest and neurologic symptoms. Although adverse events are reported fairly frequently in patients receiving triptans, they are usually mild, and few patients discontinue therapy because of them. The most serious adverse events are cardiovascular. Because of potential vasoconstrictor effects--mild and transient increases in blood pressure and mild and transient effects on coronary artery tone--triptans as a class are contraindicated in patients with established or clinically suspected cardiovascular disease, specifically ischemic heart disease and uncontrolled hypertension. Other adverse events, including the potential for drug-drug interactions, are less common. Therefore, consideration should be given to the tolerability and safety of medications before their use as abortive medications for the treatment of migraine headache.

Relief in sight for restless legs syndrome

In this issue of Neurology , Stiasny-Kolster et al. report remarkable rates of symptom relief with cabergoline, a dopamine agonist, in restless legs syndrome (RLS).1 RLS affects approximately 10% of adults and is a common cause of insomnia. Nevertheless, the majority of patients are incorrectly diagnosed by primary care physicians, and are often prescribed ineffective therapies.2 The encouraging experience with cabergoline needs to be placed into context of recent progress in deciphering the cause and improving the treatment of RLS. The Swedish physician Karl-Axel Ekbom first provided a detailed description of RLS and noted its key features: a prevalence of at least 5%; proclivity to affect pregnant women; frequent autosomal dominant inheritance; and a favorable response to iron supplementation.3 Further advances came with recognition that periodic limb movements in sleep (PLMs) occur in the tibialis anterior muscles in 85 to 95% of RLS patients. While PLMs are not specific for RLS, they represent a physiologic marker whose importance extends beyond improving diagnostic accuracy and gauging treatment response. Preceding and synchronous with PLMs are generalized, periodic elevations in somatomotor activity and cortical and autonomic arousability (e.g., transient increases in blood pressure and heart rate).4 These findings point to coordination by the brain (vs spinal cord), emphasizing that there are powerful …

White-Coat Hypertension and Risk of Stroke

The term “white-coat hypertension” (WCH; also commonly referred to as isolated office hypertension) describes the transient increase in blood pressure (BP), resulting from an alerting reaction and pressor response, observed in certain individuals when attending a clinic or doctors’ office.1 The diagnosis of WCH is usually ascribed when clinic BPs exceed 135/85 mmHg and average daytime BPs do not. WCH could be dismissed as a risk factor for stroke and other cardiovascular events, because the increase in BP is transient and may be idiosyncratic to the clinic setting.2 However, WCH may be a marker of stress reactivity per se, because surges in BP that occur in the doctor’s office are indicative of BP surges in other stressful scenarios.3 The article by Verdecchia et al featured in this edition of Hypertension 4 reports data from 6000 Italian, Japanese, and American adults. The purpose of the study was to explore the relationship between classically defined WCH and incident stroke during a median follow-up of 5.4 years. When compared with normotensive controls, a tendency for increased stroke incidence was observed in patients with WCH (unadjusted hazard ratio, 1.15). However, because the variance around the estimates of effect is large (95% confidence interval, 0.61 to 2.16), this association is not statistically significant, despite this study being the largest of its kind to date. By contrast, a statistically significantly association between ambulatory hypertension and stroke was observed (unadjusted hazard ratio, 2.01; 95% confidence interval, 1.31 to 3.08). The hypothesis that Verdecchia et al test is important because vessels in the brain may be particularly susceptible to transient elevations in BP. Furthermore, because WCH is highly prevalent,5 even a relatively small increase in stroke risk on an individual level could convey a high population-attributable risk. Although Verdecchia et al have demonstrated using …

A practical approach to persistent elevation of blood pressure in the hypertension clinic.

Patients seen with persistent elevation of office blood pressure (BP) in the hypertension clinic are common and pose a significant challenge to the hypertension specialist. These are usually patients sent to the clinic because of difficulty in achieving BP goals. In this clinical setting there is usually data available from home self measurement and ambulatory BP readings. We propose a scheme to encourage specialists to consciously consider the causes of persistent elevation of office BP. The scheme relies initially on consideration that the measured office readings are falsely elevated due to pseudohypertension, small cuff size or other equipment problems. If this is not the case then the measured office BP is truly elevated. If so, a further distinction can be made in this group into those with (1). transient office BP elevation and normal home and/or ambulatory readings and (2). elevated office and out of office readings. The first subgroup is usually called white-coat hypertension but may also be seen with transient increases in BP due to talking or other factors. The second subgroup probably is the majority of patients with persistent high office BP and reflects sustained hypertension and its own list of causes including secondary hypertension. The nature and intensity of evaluation for secondary hypertension varies depending on the clinical presentation of the patient. We recommend an explicit consideration of reasons for persistent high office BP in the hypertension clinic.

Effects of central endothelin-1 in normotensive and spontaneously hypertensive rats.

Changes in blood pressure and sympathetic nerve activity induced by local injection of endothelin-1 into the rostroventrolateral medulla were studied in narcotized stroke-prone spontaneously hypertensive rats (SHRSP) and normotensive WKY rats. Endothelin-1 produced similar biphasic response in both rat strains: a transient increase in blood pressure and sympathetic nerve activity followed by progressive hypotension and bradycardia. Pretreatment with ETB-receptor antagonist BQ788 inhibited sympathetic activation induced by endothelin-1, while pretreatment with the ETA-receptor antagonist N-acetyl-[D-Trp16]-endothelin-1 abolished the subsequent hypotension. The antihypotensive effect of ETA-receptor blockade was most effective in normotensive rats. Our findings suggest that cardiovascular disorders in SHRSP rats can be related to peculiarities in the rostroventrolateral medullar endothelin system.

Remote Recurrence Of Malignant Pheochromycytoma 14 Years After Primary Operation

The reported incidence of recurrent pheochromocytoma is 4.6% to 6.5%.1 Recurrence of pheochromocytoma more than 10 years after initial treatment is rare. We present a case of recurrent pheochromocytoma with malignant change 14 years after primary surgery. CASE REPORT A 72-year-old female had undergone left total adrenalectomy 14 years previously for adrenal pheochromocytoma. She had initially presented with frequent episodes of faintness and abdominal pain during periods of emotional stress. It is noteworthy that there were no classic signs or symptoms of pheochromocytoma, such as headache, palpitation, diaphoresis or hypertension, at initial presentation. Postoperatively followup abdominal ultrasonograms had consistently been negative. At presentation the patient reported discomfort at the previous lumbar incision several months in duration. Biochemical analyses, including 24-hour urinary vanillylmandelic acid and metanephrines, were within normal limits. Abdominal ultrasonography revealed a circumscribed 3.6 cm. hypoechoic lesion in the left suprarenal region. Computerized tomography and magnetic resonance imaging further demonstrated the mass to be highly suspicious for pheochromocytoma, which was later confirmed on ultrasound guided biopsy (see figure). A marked transient increase in blood pressure was noted at exploration. Pathological findings confirmed the presence of recurrent pheochromocytoma with additional muscular invasion, which indicated malignant change. The patient subsequently received external beam radiation therapy started on postoperative day 7. DISCUSSION