Initial Increase In Blood Pressure Research Articles

Logical Issues With the Pressure Natriuresis Theory of Chronic Hypertension.

The term "abnormal pressure natriuresis" refers to a subnormal effect of a given level of blood pressure (BP) on sodium excretion. It is widely believed that abnormal pressure natriuresis causes an initial increase in BP to be sustained. We refer to this view as the "pressure natriuresis theory of chronic hypertension." The proponents of the theory contend that all forms of chronic hypertension are sustained by abnormal pressure natriuresis, irrespective of how hypertension is initiated. This theory would appear to follow from "the three laws of long-term arterial pressure regulation" stated by Guyton and Coleman more than 3 decades ago. These "laws" articulate the concept that for a given level of salt intake, the relationship between arterial pressure and sodium excretion determines the chronic level of BP. Here, we review and examine the recent assertion by Beard that these "laws" of long-term BP control amount to nothing more than a series of tautologies. Our analysis supports Beard's assertion, and also indicates that contemporary investigators often use tautological reasoning in support of the pressure natriuresis theory of chronic hypertension. Although the theory itself is not a tautology, it does not appear to be testable because it holds that abnormal pressure natriuresis causes salt-induced hypertension to be sustained through abnormal increases in cardiac output that are too small to be detected.

Use of local anesthesia in ear surgery: technique, modifications, advantages, and limitations over 30 years’ experience

Background Local anesthesia (LA) is safe and well established for a variety of ear operations. It has many advantages compared with general anesthesia (GA). Objective This article is intended to be a comprehensive reference for those who use this art, in which we have more than 30 years of experience. We also aimed to find out the effect of LA on blood pressure (BP) and heart rate (HR), operative time, time of anesthesia with different adrenaline concentrations, and patient satisfaction with LA. Patients and methods This was a retrospective study of our experience in the technique of LA in more than 2600 patients spanning more than 30 years, along with modifications introduced. Additional prospective trials were also conducted. BP and HR were monitored during LA injection in 200 patients. The calculated operative time was compared between two groups of 21 patients each: the first group was operated upon under LA and the other under GA. Anesthesia time was calculated for LA with different adrenaline concentrations (1 : 20 000–1 : 200 000 and 0% or no adrenaline) by means of injections over both the mastoid and the forearm on five volunteers. Patient satisfaction was measured using postoperative questionnaire in 200 patients. Results Patients showed initial increase in BP due to apprehension, which was abolished with diazepam; a second increase in BP and HR occurred after LA injection by 3–10 min. LA statistically significantly shortened the operative time compared with GA. Time of anesthesia was longer using anesthetic solution with higher adrenaline concentration and was longer on the mastoid as compared with the forearm. Finally, 92% of the patients showed satisfaction from the procedure. Conclusion LA is a safe and effective way of anesthesia in ear surgery, allowing intraoperative testing of hearing, facial nerve action, and eustachian tube patency. With high adrenaline concentration, it allows excellent hemostasis, shortens the operative time, and increases the time of anesthesia, allowing probable prolonged postoperative analgesia and is well tolerated by the patients.

Abstract 073: Expression of Axl in Innate Immune Cells Contributes to Kidney Dysfunction and Onset of Hypertension

Introduction: We previously reported that expression of the receptor tyrosine kinase Axl in hematopoietic cells is critical for kidney dysfunction in early hypertension. Here we investigated the role of Axl expression in innate immune cells in deoxycorticosterone acetate (DOCA)-salt induced hypertension. Methods and Results: RAG1-/- mice lack adaptive immune cells and displayed the same (~25 mmHg) increase in systolic blood pressure (BP) as C57BL/6J mice after 1 week of DOCA-salt. While in metabolic cages RAG1-/- drank more (14.3±0.9 mL) than C57BL/6J mice (10.6±2.5 mL) per day after 1 week of DOCA-salt. Ultrasound imaging confirmed that RAG1-/- had ~20 % larger kidneys vs. C57BL/6J mice after DOCA-salt. RAG1-/- kidneys accumulated 2 times more fluid (2.8±0.1 %) compared to C57BL/6J mice (1.4±0.5 %) after DOCA-salt. Flow cytometry on kidneys from RAG1-/- confirmed absence of T and B lymphocytes, while DOCA-salt increased presence of macrophages (1.1±0.3 x10 9 ) compared to C57BL/6J mice (0.6±0.1 x10 9 ). We successfully generated Axl/RAG1 double knockout mice and subjected the littermates to 1 week of DOCA-salt. Increases in systolic BP were the same in Axl/RAG1+/+ and Axl/RAG1-/- littermate mice. No differences were found in kidney volumes between the Axl/RAG1 genotypes as well. However, 24 hrs excretion volumes increased in Axl/RAG1-/- (50±6 %) compared to Axl/RAG1+/+ (31±6 %) littermates. Finally, renal artery blood flow velocity (611±52 mm/s) and resistive index (0.62±0.03) were reduced in Axl/RAG1+/+ but not in Axl/RAG1-/- mice (665±45 mm/s and 0.68±0.01, respectively) when compared to their controls. Conclusions: Our findings suggest that mice lacking lymphocytes compensate by increasing kidney macrophages that contribute to initial increase in BP. Depletion of Axl in innate immune cells partially reverses kidney dysfunction by improving renal artery function in early hypertension.

Cardiovascular effects of N‐butylscopolammonium bromide and xylazine in horses

N-butylscopolammonium bromide (NBB) and xylazine are commonly used medications for the treatment of spasmodic colic and other forms of abdominal pain in horses. Both NBB and xylazine exert significant effects on the cardiovascular system and other vital systems of horses. To evaluate the effects of i.v. administration of NBB, xylazine, and the combination of NBB and xylazine on heart rate, other commonly measured physiological parameters, cardiac rhythm and blood pressure. Six mature horses of mixed breed were used. In a random cross-over design, each horse was given 0.3 mg/kg bwt of NBB i.v., 0.25 mg/kg bwt xylazine i.v., and a combination of 0.3 mg/kg bwt NBB and 0.25 mg/kg bwt xylazine. Heart rate, physiological parameters, cardiac rhythm and indirect blood pressure were recorded at timed intervals before and 60 min following administration. Heart rate and blood pressure were significantly elevated immediately following administration of NBB or NBB with xylazine. Administration of NBB with xylazine resulted in significantly greater initial and peak blood pressure values than with NBB alone. Administration of xylazine resulted in a decrease in heart rate, with an initial increase in blood pressure followed by a decrease in blood pressure. Sinus tachycardia was seen with NBB, and NBB and xylazine administration. First and second degree atrioventricular block was identified with xylazine administration. Ventricular tachycardia was identified in one horse following NBB and xylazine administration. Results of this study suggest that the effects of administration of NBB alone or in combination with xylazine to horses with colic, especially to those with systemic cardiovascular compromise, should be considered carefully to assess condition and predict prognosis accurately, and to avoid potential adverse effects.

Sex of the Animal Impacts Responses to Angiotensin II, Oxidative Stress Levels, and Nitric Oxide Bioavailability

HomeHypertensionVol. 57, No. 5Sex of the Animal Impacts Responses to Angiotensin II, Oxidative Stress Levels, and Nitric Oxide Bioavailability Free AccessLetterPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessLetterPDF/EPUBSex of the Animal Impacts Responses to Angiotensin II, Oxidative Stress Levels, and Nitric Oxide Bioavailability Krystal N. Brinson and Jennifer C. Sullivan Krystal N. BrinsonKrystal N. Brinson Search for more papers by this author and Jennifer C. SullivanJennifer C. Sullivan Search for more papers by this author Originally published28 Feb 2011https://doi.org/10.1161/HYPERTENSIONAHA.111.171017Hypertension. 2011;57:e18Other version(s) of this articleYou are viewing the most recent version of this article. Previous versions: January 1, 2011: Previous Version 1 To the Editor:Oxidative stress has been implicated in the pathogenesis of renal and cardiovascular diseases; however, there is still much to be learned. It is against this background that we read with great interest the article titled, “Superoxide Dismutase 1 Limits Renal Microvascular Remodeling and Attenuates Arteriole and Blood Pressure Responses to Angiotensin II via Modulation of Nitric Oxide Bioavailability,” by Carlström et al.1 The goal of this article was to determine the functional role of superoxide dismutase 1 (SOD1) in regulating renal microvascular function and blood pressure responses to angiotensin (Ang) II. The authors found that SOD1 knockout mice had a greater initial increase in blood pressure to chronic Ang II compared with wild-type control mice. In addition, renal afferent arterioles from SOD1 knockout mice were significantly more sensitive to acute Ang II–induced vasoconstriction compared with wild type, whereas arterioles from SOD1 transgenic mice were less sensitive to Ang II versus controls. Altered vascular responsiveness was likely attributed to low levels of NO bioavailability in arterioles from SOD1-knockout mice and enhanced levels of superoxide.Although the authors are to be commended on their excellent work, we would like to call attention to the fact that experiments were conducted using both male and female SOD1-transgenic, SOD1 knockout, and wild-type littermate mice with an equal distribution of both sexes in all of the experiments. Based on known sex differences in blood pressure and vascular responses to Ang II,2 sex differences in NO bioavailability,3 and sex differences in oxidative stress and antioxidant potential,4 the inclusion of both sexes may be a confounding factor in the study. In fact, if only males had been included, the differences between the SOD1-knockout and transgenic mice and the appropriate wild-type control groups may have been more dramatic. For example, female experimental animals have been shown to be less sensitive to Ang II–induced hypertension, therefore, it would be interesting to know whether the blood pressure data in Figure 2 of their article included 2 males and 3 females or 3 males and 2 females. The inclusion of both sexes may also contribute to the greater variability in the blood pressure data with Ang II infusion. In addition, we recently published that female SOD3 knockout mice maintain total SOD activity because of a compensatory upregulation of SOD1 activity.5In closing, although we applaud the authors on the inclusion of females in their study, we encourage them to examine the data between the sexes separately. Based on existing data in the literature, they may find additional novel findings based on the sex of the animal.Krystal N. Brinson Vascular Biology Center Georgia Health Science University Augusta, GAJennifer C. Sullivan Vascular Biology Center and Department of Pharmacology and Toxicology Georgia Health Science University Augusta, GASources of FundingSupported by NIH1R01 HL-093271-01A1 to J.C.S.DisclosuresNone.FootnotesLetters to the Editor will be published, if suitable, as space permits. They should not exceed 1000 words (typed double-spaced) in length and may be subject to editing or abridgment.

Autonomie Mechanisms and Therapeutic Implications of Postural Diabetic Cardiovascular Abnormalities

Cardiovascular autonomic neuropathy (CAN) is a disorder of progressive autonomic dysfunction (AD) associated with diabetes and other chronic diseases. Orthostatic hypotension (OH) is one of the most incapacitating symptoms of CAN and AD. AD in OH can include sympathetic withdrawal (SW). To detect and diagnose SW, parasympathetic and sympathetic changes must be clearly differentiated from each other. This is accomplished by means of the novel autonomic nervous system (ANS) method based on the simultaneous spectral analyses of respiratory activity (RA) and heart rate variability (HRV). We performed autonomic profiling of 184 (142 females) consecutive, arrhythmia-free patients with type 2 diabetes using the ANX-3.0 autonomic monitoring system. The patient cohort included 86 (64 female) patients for whom an alpha(1)-agonist was the only drug changed and increased from one test to the next; 37 (33 female) for whom the alpha(1)-agonist was discontinued; and 61 (45 female) who were on an alpha(1)-agonist, but for whom no drug changes were made. The tests averaged 3.1 +/- 1.4 months apart; midodrine (ProAmatine) was the alpha(1)-agonist prescribed. Of the group, 99 patients also had hypertension and 47 also had cardiovascular disease. No patient had supine hypertension. Changes in parameters from the HRV (without respiration) and ANS methods were compared with changes in heart rate and blood pressure (BP) as measured from one test (test N) to the next (test N + 1). SW with a BP drop of less than the clinical definition may be a trend that can be an early indicator of orthostasis. In this study, patients were treated with low-dose, short-term alpha(1)-agonist (vasopressor) therapy, which tended to correct the abnormal trend of SW with a drop in BP. Included in the findings was a systolic BP trend in response to vasopressor therapy of an (expected) initial increase in BP followed by an eventual decrease in systolic BP as SW was reversed. The ANS method enables quantitative assessment of CAN by independently and simultaneously quantifying the two branches of the ANS, sympathetic and parasympathetic. The ANS method modifies standard spectral analysis of HRV (without RA analysis) by incorporating spectral analysis of RA. The ANS method appears to model the normal and abnormal responses to upright posture and changes in vasopressor therapy with greater fidelity than the HRV method. Independent, simultaneous assessment of progressive parasympathetic and sympathetic dysfunction, autonomic imbalance, and responses of the two ANS branches to therapy seems to enable early detection and early intervention. Orthostasis, by way of example, illustrates that frequent, sensitive assessments of both ANS branches can improve the negative outcomes associated with CAN.

Pattern of changes in central and cerebral hemodynamics in the basilar artery during active orthostasis in healthy individuals

We studied changes in cerebral and central hemodynamics during active orthostatic load in 26 healthy men aging 20-26 years. Two types of central hemodynamics were revealed: progressive increase in blood pressure throughout the test (type 1) or initial blood pressure increase followed by its decrease with maximum increase in diastolic blood pressure (type 2). The reactions of cerebral hemodynamics to active orthostasis in healthy individuals manifested in reduced cerebral blood flow in the basilar artery. The decrease in blood flow rate in the basilar artery during active orthostasis was associated with vasoconstriction of pial vessels of the vertebrobasilar basin and with the increase in respiratory volume.

Acute Blood Pressure Effects and Chronic Hypotensive Action of Calcimimetics in Uremic Rats

A previous study in subtotally nephrectomized (SNX) rats suggested beneficial effects of the calcimimetic R-568 beyond the control of mineral metabolism. This study analyzed potential blood pressure (BP)-lowering effects of R-568. Male Sprague-Dawley rats received two-stage subtotal nephrectomy or sham operation. Telemetry devices were inserted into the abdominal aorta, and BP was measured every 5 min. R-568 (20 mg/kg per d) or solvent was infused for 4 wk followed by once-daily subcutaneous injections for 2 wk. Total body sodium was measured by neutron activation analysis. The uremia-induced increase of mean arterial pressure from baseline to day 42 in SNX solvent rats (103+/-5 to 128+/-14 mmHg, P=0.006) was attenuated by R-568 (104+/-5 to 111+/-8 mmHg; P<0.0001 for difference of slopes). The circadian rhythm was abrogated in SNX rats and not restored by R-568. In sham-operated rats, R-568 had only a minor transient antihypertensive effect. R-568 injection induced a transient rise of mean arterial pressure by 23+/-4 and 26+/-10 mmHg in sham and SNX rats but only by 9+/-3 and 10+/-5 mmHg in solvent-treated rats (P<0.01 versus baseline and solvent versus R-568). Plasma angiotensin-converting enzyme activity and aldosterone levels were similar; food intake and physical activity did not differ throughout the study. In healthy rats, total body sodium was higher after 14 d of R-568 compared with solvent infusion (37.1+/-4 versus 32.5+/-1.4 mmol/kg; P=0.01). The calcimimetic R-568 causes an initial BP increase in sham-operated and uremic rats, which in uremic rats is followed by a marked and sustained antihypertensive effect.

Vascular gap junctions and implications for hypertension

Four connexin (Cx) molecules, namely Cx37, Cx40, Cx43 and Cx45, are expressed in the gap junctions that exist within and between the cellular layers of arteries. Endothelial cells are well coupled by large gap junctions expressing Cx37, Cx40 and, to a lesser extent, Cx43, whose expression may be more subject to regulation by physical factors. Smooth muscle cells are more heterogeneously coupled by gap junctions that are small and rare. The identity of the Cx expressed in the media may vary among different arteries. Myoendothelial gap junctions are small and more common in resistance arteries with fewer layers of smooth muscle cells. Given the small size of these gap junctions and the rapid turnover rate of Cxs, homocellular coupling in the media and heterocellular coupling between the cell layers may be subject to more dynamic control than coupling in the endothelium. Vascular gap junctions have been implicated in a number of vasomotor responses that may regulate vascular tone and blood pressure. These include the mechanism of action of the vasodilator, endothelium-derived hyperpolarizing factor (EDHF), the myogenic constriction to intramural pressure increase, the spontaneous or agonist-induced vasomotion of arteries and arterioles and the spreading vasodilation and constriction observed in microcirculatory networks. Few data are available on Cx expression in the media of resistance arteries during hypertension. Changes in the expression of Cx43 described in the media of the aorta of hypertensive rats vary with the hypertensive model studied and are likely to represent adaptations to structural changes in the vascular wall. In contrast, in the endothelium of the caudal and mesenteric arteries of spontaneously hypertensive rats, expression of Cxs is significantly decreased compared with arteries from normotensive rats and this decrease is reversed by inhibitors of the renin-angiotensin system. During hypertension, the activity of EDHF is decreased in the mesenteric artery, but this occurs much later than the initial increase in blood pressure and the decrease in endothelial Cxs, suggesting that changes in EDHF may not be causally related to hypertension or to the changes in endothelial Cxs. Upregulation of the myogenic response and the incidence of vasomotion has been reported in hypertension. Little is currently known of the effects of hypertension on spreading vasomotor responses. Deletion of specific Cxs in genetically modified mice is complicated by neonatal lethality or coordinate regulation and compensatory changes in the remaining Cxs. Nevertheless, mice in which Cx40 has been deleted are hypertensive and spreading vasodilatory responses are significantly impaired. Determination of a role for specific Cxs in the control of blood pressure must await the development of animals in which Cx expression can be modulated in a more complex temporal and tissue-specific manner.

Differential blood pressure and heart rate responses to supramedullary brain stimulation in cats.

The purpose of this study was to compare the cardiovascular responses to electrical stimulation of different supramedullary brain regions. Arterial blood pressure (BP) and heart rate (HR) effects were elicited by electrical stimulation of the lateral hypothalamus (LH), mamillary bodies (Mm), substantia nigra (SN), globus pallidus (GP), and the subthalamic nucleus (Sub) in conscious, freely moving cats. Pressor responses were obtained from all of these regions. The higher intensity of stimulation the higher increase in BP and HR was obtained. However, clear-cut differences occurred in the effects both during and after the termination of stimulations. Namely, a continuous increase in BP and HR was obtained from the LH and SN. In contrast, the initial increase in BP and HR was followed by a reduction compared to the peak value of the effects of stimulation in the GP and the Sub. However, the BP and HR never reduced to the pre-stimulaion level during the stimulation. Also the changes following the cessation of stimulation at the different brain loci were dissimilar. The BP and HR either returned gradually to the pre-stimulation level, or long-lasting oscillation occurred. The electrical activity of the nucleus of the solitary tract (NTS) and the vagus nerve co-varied with the changes in BP and HR. It is concluded that the supramedullary stimulations produce differential cardiovascular effects, and these effects are modified by the baroreflexes that are activated by the electrically elicited rise in blood pressure.

Role of Nitric Oxide in Buffering Short-Term Blood Pressure Fluctuations

Blood pressure instability may promote cardiovascular morbidity. Recent data suggest a role of nitric oxide in stabilizing arterial blood pressure. A rise in blood pressure enhances endothelial shear stress and nitric oxide release. The resulting vasodilation antagonizes the initial increase in blood pressure. This system can respond within 2-10 seconds.

Brain nitric oxide changes after controlled cortical impact injury in rats.

Nitric oxide (NO) and the NO end products, nitrate and nitrite, were measured at the impact site after a 5-m/s, 3-mm deformation controlled cortical impact injury in rats. Immediately after the impact injury and the NO and microdialysis probes could be replaced, there was an increase from baseline in NO concentration of 83 +/- 16 (SE) nM, compared with 0.5 +/- 4 nM in the sham injured animals (P < 0.001). This marked increase in NO occurred at the time of the initial rise in blood pressure (BP) and intracranial pressure (ICP) in response to the injury. After the initial increase in BP and ICP, the BP decreased and stabilized at a value which was approximately 20 mmHg below the preinjury values, and ICP plateaued at an average value of 20 mmHg, compared with 8 mmHg in the sham-injured animals. This provided an average cerebral perfusion pressure of 40-50 mmHg, compared with 65-75 mmHg for the sham-injured animals. These values were relatively constant for the remainder of the 3-h monitoring period. The NO values also stabilized during this time period. By 1 h after the impact injury the NO concentration measured directly using the NO electrode had decreased from baseline values by an average value of 25 +/- 6 nM. NO concentration remained significantly lower than baseline values throughout the remainder of the 3-h monitoring period. The concentration of nitrate/nitrite in the dialysate fluid also decreased by an average value of 341 +/- 283 nM 20-40 min after the injury. Dialysate nitrite/nitrate concentrations remained less than the preinjury baseline values throughout the remainder of the 3-h monitoring period. Preinjury treatment with L-nitro-arginine methyl ester (L-NAME) blunted the injury-induced increase in NO and resulted in more severe immediate intracranial hypertension and more severe systemic hypotension at one hour after injury. Mortality was also 67% with L-NAME pretreatment, compared with 1% in untreated animals.

Serotonin-4 receptor antagonists reverse cocaine-induced cardiac arrhythmia

The effect of the 5-HT 4 antagonists GR113808A and GR125487D on cocaine-induced cardiac arrhythmia was examined in the rat. Cocaine alone, given IV at a rate of 2 mg kg every 5 min, produced an initial increase in blood pressure followed by a severe drop in pressure and bradycardia. Sustained ventricular fibrillation was noted after 6–12 mg kg cocaine and quickly progressed to asystole. Pretreatment with both GR113808A and GR125487D antagonized these effects in a dose-dependent manner. When given after the onset of arrhythmia, both drugs reversed the cocaine-induced arrhythmia's. Thus, the 5-HT4 antagonists may be useful in the treatment of cocaine toxicity.

Brain ANG II and prostaglandins mediate the pressor response after central blockade of nitric oxide synthase

Central inhibition of nitric oxide synthase (NOS) by intracerebroventricular (i.c.v.) administration of N G-nitro- l-arginine methyl ester (L-NAME; 150 μg/5 μl) to conscious rats produced a biphasic pressor response characterized by an initial transient increase within 5 min, and a delayed response starting between 60–90 min. The effect was stereospecific, as D-NAME (250 μg/5 μl) did not modify the resting arterial blood pressure, nor did l-arginine (323 μg/5 μl, i.c.v.), indicating the substrate for NOS is not rate-limiting. Intracerebroventricular pretreatment with losartan (25 μg/5 μl), a non-peptide antagonist of the angiotensin II AT 1 receptor subtype, or indomethacin (100 μg/5 μl), a blocker of cyclooxygenase, however, prevented the initial increase in blood pressure without affecting the delayed pressor response. In contrast, neither intravenous losartan (10 mg/kg b.wt) nor prazosin, an α 1 adrenergic receptor antagonist, at doses of 5 μg/5 μl (i.c.v.) or 0.3 mg/kg b.wt (i.v.) were effective in altering the pressor responses. These results indicate that centrally produced NO maintains the resting arterial blood pressure at least partially through modulation of the brain angiotensin system and prostaglandins.

The blocking effects of tolazoline and propranolol on axial movements of incisor teeth and on changes in arterial blood pressure induced by adrenaline in rats.

Axial tooth movements and arterial blood pressure were measured following intravenous injection of adrenaline, 1hr before, and 1 and 2hr after the injection of tolazoline (an α-adrenergic blocking agent) or propranolol (a β-adrenergic blocking agent). The initial increase in blood pressure induced by adrenaline was significantly suppressed and the successive decrease in blood pressure was markedly enhanced by pretreatment with tolazoline. In contrast to blood pressure changes, the initial extrusive tooth movement induced by adrenaline was not suppressed, and successive intrusive tooth movements induced by adrenaline were not potentiated, but suppressed. The initial increase in blood pressure induced by adrenaline was enhanced and the successive decrease in blood pressure was suppressed by pretreatment with propranolol. On the other hand, the initial extrusive tooth movement induced by adrenaline was not significantly potentiated, but successive intnsive tooth movements induced by adrenaline were markedly suppressed. Pressure within the socket that may induce axial tooth movements might be regulated by various factors, such as resistance of the blood vessels, blood flow in the socket, and systemic arterial blood pressure, all of which are liable to change following an injection of adrenaline under the influence of α-or β-adrenergic blockers.

Decreased ventilatory response to hypoxia in sedated newborn piglets prenatally exposed to cocaine

OBJECTIVE: Infants exposed to cocaine in utero have been reported to have a higher incidence of apnea and altered ventilatory response to carbon dioxide and hypoxia. We investigated whether in utero cocaine exposure results in greater ventilatory depression during hypoxia in piglets. METHODS: Cocaine hydrochloride, 1.0 or 2.0 mg/kg given intramuscularly, or saline solution was administered daily to pair-fed pregnant sows during the last month of gestation. Thirteen cocaine-exposed piglets (mean ± SD: age, 4.4 ± 1.3 days; weight, 2.10 ± 0.10 kg) and 15 saline solution-exposed piglets (age, 4.6 ± 1.1 days; weight, 2.32 ± 0.42 kg) were studied under chloral hydrate sedation. Minute ventilation (v̇ E), arterial blood pressure (BP), heart rate (HR), oxygen consumption (v̇ O 2), and arterial blood gases were measured in room air. During hypoxia (fraction of inspired oxygen = 0.10), the values for v̇ E, BP, and HR were obtained at 1, 5, and 10 minutes, v̇ O 2 was calculated during the last 5 minutes, and arterial blood gas samples taken after 10 minutes. RESULTS: Basal v̇ E did not differ between saline solution- and cocaine-exposed animals. The increase in v̇ E at 1 minute of hypoxia was also similar. However, at 5 and 10 minutes of hypoxia, v̇ E was significantly lower in the cocaine group than in the saline group (6% ± 9% and 4% ± 10% vs 15% ± 13% and 21% ± 14%; p <0.02). Mean baseline BP and the initial increase in BP during hypoxia were not different between groups. However, BP remained increased throughout hypoxia only in the saline solution-exposed animals ( p <0.05). Changes in HR, v̇ O 2, arterial oxygen tension, and base excess during hypoxia were similar between groups. CONCLUSIONS: These results show a decrease in the ventilatory response to hypoxia in newborn piglets prenatally exposed to cocaine. This change is most likely to be centrally mediated because the initial hypoxic hyperventilation was not modified by the intrauterine cocaine exposure. This decrease in ventilation cannot be explained by changes in metabolic rate or in cardiovascular or acid-base status. (J P EDIATR 1996;128:389-95)

Cardiovascular responses at the onset of static exercise in patients with dual-chamber pacemakers.

Cardiac output (CO) responses to exercise can be altered by ventricular pacing in pacemaker-dependent patients. The relative contributions of CO and peripheral vascular resistance (PVR) toward the initial increase in blood pressure with the initiation of static exercise were investigated in eight otherwise healthy pacemaker-dependent subjects [age 24 +/- 2 yr (range 17-37 yr)]. Beat-by-beat measures of heart rate (HR; electrocardiography), mean arterial pressure (MAP), and CO derived from stroke volume (SV) (CO = HR.SV; 2-D echocardiography) were determined during the first 20 s of a one-legged static knee extension performed at 20% maximal voluntary effort by using three pacing modalities: dual pacing and sensing mode (DDD, i.e., normal physiological HR response), fixed at resting HR (DOO-R), and fixed at peak exercise HR (DOO-E), as previously achieved during 5 min of sustained contraction in the DDD mode. There were no differences in MAP, CO, or PVR (PVR = MAP/CO) between modes at rest (P > 0.05). With DOO-E pacing, SV was lower at rest compared with the other modes and increased with exercise (P < 0.05). Although there were no significant increase in MAP or CO during DOO-R pacing, both variables were elevated by leg contraction during DDD and DOO-E pacing (P < 0.05), with no significant change in PVR. Additionally, the CO and MAP increases were significantly greater with DOO-E pacing (P < 0.05). Thus the magnitude of the initial increase in arterial pressure at the onset of mild one-legged static exercise was dictated by the changes in CO as PVR remained unchanged.

Longitudinal changes during the development of hypertension in rats fed excess chloride and sodium.

The effects of supplemental NaCl, KCl, and Na acetate on the blood pressure of weanling rats fed semipurified diets and diets based on naturally high salt products, like cottage cheese, were examined in two studies. Within 2 weeks of initiation of dietary treatments, rats fed supplemental chloride had elevated blood pressure and lowered plasma renin activity, which persisted throughout the 8-week study. The effect of supplemental sodium on blood pressure was not significant until after 6 weeks of dietary treatment. The initial increase in blood pressure preceded the slowed growth observed in rats fed excess chloride or sodium. Urinary volume and urinary excretion of calcium, magnesium, phosphorus, sodium, and chloride were increased when supplemental chloride or sodium was fed, but tissue electrolyte and plasma atrial natriuretic peptide concentrations remained constant. Two changes preceded the rise in blood pressure: rats fed supplemental chloride had enlarged kidneys, and those fed supplemental sodium had elevated hematocrits, suggesting a transient shift among fluid compartments, after only 6 days of treatment. These data suggest that the hypertension induced by ingestion of supplemental (14.6 mg CI/g of diet) chloride is mediated by changes in renal function. Ingestion of excess sodium depressed bone magnesium concentrations in Study 1 and after 24 days in Study 2; the impact of this "relative" magnesium depletion on blood pressure deserves further study.

The role of nitric oxide in endotoxic shock: effects of NG-monomethyl-L-arginine.

The role of nitric oxide (NO) in the changes in blood pressure and plasma levels of nitrate and nitrite (NOx) and alanine aminotransferase (ALT) were determined over a 5-h period in anesthesized rats after intravenous administration of S. typhosa endotoxin (LPS, 4 mg/kg). Rats treated with LPS showed a sustained fall in blood pressure accompanied by an increase in plasma NOx and ALT. Forty percent of these rats died during the experiment. There was no change in blood pressure in rats treated with dexamethasone (1 mg/kg) 1 h before and 2 h after LPS and the increase in NOx and ALT was significantly inhibited. None of the rats in this group died. Administration of 10 mg/kg of NG-monomethyl-L-arginine (L-NMMA) prevented the fall in blood pressure and partially prevented the increase in NOx and ALT. None of the animals in this group died. In contrast, 300 mg/kg of L-NMMA caused an initial increase in blood pressure followed by a rapid fall and enhanced the increase in ALT while abolishing the elevation of NOx. All of these animals died before the end of the experiment. However, when rats treated with high doses of L-NMMA were given a continuous infusion of S-nitroso-N-acetylpenicillamine (SNAP, 300 micrograms/kg/h), the blood pressure was maintained at control levels and no mortality was observed.(ABSTRACT TRUNCATED AT 250 WORDS)

Evidence for a dissociation between cardiovascular and behavioral reactivity in the spontaneously hypertensive rat

Spontaneously hypertensive rats of the Okamoto strain (SHR) were compared with normotensive rats of the Wistar-Kyoto strain (WKY) on the acoustic startle response in rats prepared for simultaneous blood pressure recordings. Blood pressure was continuously recorded by means of an indwelling cannula in the caudal tail artery. The presentation of the startle stimulus caused a blood pressure response in both strains consisting of an initial increase in blood pressure followed by a decrease and after that a longer lasting, but less pronounced second increase in pressure. The startle-elicited increase in blood pressure was significantly elevated in SHRs and at the same time the acoustic startle response was depressed as compared to WKY rats. These data indicate a dissociation between cardiovascular and behavioral reactivity in the SHR.