Intravenous Injection Of Sodium Nitroprusside Research Articles

Convenient Application of a Compact-Type Magnetic Resonance Imager with Blood Pool Contrast Agent Gadolinium-Conjugated Dextran to Assess Vascular Abnormalities in Experimental Animals.

Vascular lesions are symptomatic of lifestyle-related diseases and include blood clots, coarctations, aneurysms, and apoplexy. Furthermore, increased blood vessel permeability is usually observed in tumors. To develop therapeutic drugs treating vascular lesions and tumors, methods with which the vascular abnormalities can be readily assessed in experimental animals are necessary. In this paper, a laboratory-size magnetic resonance imaging (MRI) system with permanent magnets, a compact-type MRI, was used to assess vascular abnormalities. Blood vessels in the head of a mouse were clearly visualized with the compact-type MRI in combination with gadolinium-diethylenetriamine-N,N,N',N″,N″-pentaacetic acid chelate (Gd-DTPA)-linked dextran (Gd-Dex) as blood pool contrast agents. The rat middle cerebral artery was imaged, and artery occlusion was identified. The difference between normal and occluded rats became more apparent upon intravenous injection of sodium nitroprusside, a nitric oxide (NO) donor. The system also visualized poor circulation in a rat saphenous artery by femoral artery occlusion. In a tumor-bearing mouse, a compact-type MRI visualized accumulation of Gd-Dex similar to that of small molecular Gd-DTPA, in the rim of tumor. Gd-Dex accumulation was more consistent than that of Gd-DTPA. Tumor vasculature was characterized by estimating the plasma-to-tumor interstitial tissue transfer constant, Ktrans, of Gd-Dex and fractional plasma volume, Vp, using image data. These results demonstrate the efficacy of a compact-type MRI in combination with Gd-Dex for vascular abnormality assessment in both mice and rats.

Bardet Biedl syndrome genes are required for autonomic control of the circulation

Bardet Biedl syndrome (BBS) is a pleiotropic autosomal recessive disorder with several features including hypertension and cardiovascular disease. The 16 Bbs genes identified so far have been implicated in the regulation of several physiological functions. Here, we used the knock‐in Bbs1M390R mouse model that phenocopy human BBS to test the hypothesis that Bbs genes are important for autonomic function. Baroreflex sensitivity (BRS) was examined in conscious state using the responses of renal sympathetic activity, arterial pressure and heart rate (HR) to the sequential intravenous injection of sodium nitroprusside and phenylephrine (PE). Notably, the maximum gain of the baroreflex was reduced in the Bbs1M390R mice (0.8±0.5%) vs. controls (3.3±0.9%, P<0.01). Direct recording of baroreceptor activity from the aortic depressor nerve (ADN) during PE‐induced hypertension which provides another measure of BRS revealed attenuated ADN baroreflex response in Bbs1M390R mice (6±2%) vs. controls (12±3%, P<0.05). Finally, analysis of the central component of the baroreflex with electrical stimulation (40 Hz) of the ADN showed an attenuated HR reflex response in Bbs1M390R mice (−47±16 bpm) vs. controls (−88±15 bpm, P<0.03) indicating that the impairment in BRS in BBS mice is centrally‐mediated. Our data demonstrates that Bbs genes are critically involved in the autonomic regulation of the cardiovascular function.

Effect of Acute Increase in Blood Pressure on Intraocular Pressure in Pigs and Humans

To study the effect on intraocular pressure (IOP) of a sudden increase in blood pressure (BP) and of changes in partial pressure of CO(2) (pCO(2)). Two experimental studies were conducted: in pigs (n = 7), where BP was reduced by intravenous injection of sodium nitroprusside and increased by injection of angiotensin II; and in humans (n = 17 healthy subjects), where BP was increased by two types of isometric exercise (squatting and handgripping) performed for 2 minutes; IOP and pCO(2) were measured every 30 seconds during separate tests (rest, hyperventilation, isometric exercise) and then after 1, 3, 6, and 10 minutes of rest. In pigs, there is a linear relationship between BP and IOP variations: DeltaIOP = 1.21 DeltaBP - 0.14 (P < 0.001). In humans, this linear relationship is as follows: DeltaIOP = 0.40 DeltaBP + 0.85 (P < 0.001) for squatting and DeltaIOP = 0.54 DeltaBP + 0.55 (P = 0.02) for handgripping. BP and IOP increases are greater with squatting than with handgripping (53% vs. 46%, P = 0.05 and 46% vs. 35%, P = 0.03, respectively). Handgripping causes a greater fall in capnia than squatting does (P = 0.02). Capnia and IOP are positively correlated (P < 0.001). The pharmacological approach in animals and the study of isometric exercise in humans show that IOP rises significantly and rapidly with kinetics close to those of BP, and the two values are linearly related. The absence of variation in capnia and the greater increase in BP during squatting may explain the greater increase in IOP during this exercise compared to handgripping.

Sympathoexcitatory outflow from the Rostral Ventrolateral Medulla is attenuated in aged Wistar‐Kyoto Rats

The rostral ventrolateral medulla (RVLM) vasomotor neurons are responsible for maintaining the tonic excitation of sympathetic preganglionic neurons. It is well known that the aging causes the physiological alternation in cardiovascular regulation. However, the cardiovascular influence of central vasomotor neurons in the advanced aged animals are not fully examined. In this study, using more than 80 weeks old Wistar‐Kyoto rats (WKY) as high aged model, we sought to determine the cardiovascular response of RLVM in glutamatergic stimulation. In alpha‐chloralose‐anesthetized animals, microinjection of glutamate into unilateral RVLM were performed. In elderly WKY rats, although the intravenous injection of sodium nitroprusside or phenylephrine evoked similar response of the groups of animals in 16–20 weeks old, the response evoked by microinjection of glutamate into RVLM were smaller than that of control. These results suggest the sympathoexcitatory influence from RVLM is attenuated in advanced aged animals.

The Penile Erection Efficacy of a New Phosphodiesterase Type 5 Inhibitor, Mirodenafil (SK3530), in Rabbits with Acute Spinal Cord Injury

Mirodenafil (SK3530) is a new potent and selective inhibitor of cGMP-specific phosphodiesterase type 5 (PDE5). Recent clinical trials have demonstrated that mirodenafil is an effective treatment for erectile dysfunction. Its mechanism of action is enhancement of nitric oxide (NO) induced cGMP formation resulting in significant relaxation of the corpus cavernosum (CC). The aim of this study was to investigate the oral efficacy of mirodenafil in an acute spinal cord-injured rabbit model. Mirodenafil or sildenafil citrate was given orally to male rabbits with a surgical transection of the spinal cord at the L2-L4 lumbar vertebra or ischemic-reperfusion spinal cord injury (SCI). Erections were evaluated in a time-course manner by measuring the length of the uncovered penile mucosa. In the transection SCI model, penile erections were induced at 0.3, 1 and 3 mg/kg of mirodenafil but sildenafil only showed an erectile response at 3 mg/kg. The effects of 1 and 3 mg/kg of mirodenafil were significantly increased by intravenous injection of sodium nitroprusside (SNP), a nitric oxide donor. In the ischemic-reperfusion injury model, 3 mg/kg of either mirodenafil or sildenafil produced a penile erection response. After injection of SNP, the lengths of immediate penile erections were significantly increased in the 1 and 3 mg/kg mirodenafil and 3 mg/kg sildenafil groups. The onset of erectile activity was faster with mirodenafil than with sildenafil citrate. These results demonstrate that mirodenafil may be useful for treating erectile dysfunction in patients with a spinal cord injury.

DA-8159 has erectile potentials much longer than the plasma half-life in a conscious rabbit model

DA-8159 is a pyrazolopyrimidinone derivative which is a potent and selective phosphodiesterase type 5 inhibitor. The efficacy of oral DA-8159 has been demonstrated in conscious and spinalized rabbits by its enhancement of nitric oxide-induced erections. The aim of this study was to investigate the time dependency of this efficacy on its plasma concentration in rabbits. DA-8159 was given orally to normal rabbits at a dose of 10 or 30mg/kg in order to determine its pharmacokinetic parameters. After then, to investigate the relationship between penile erectile activity and plasma half-life, a dose of 10mg/kg DA-8159 was administered and the erectile response was examined in a time-course manner by measuring the length of the uncovered penile mucosa after the intravenous administration of sodium nitroprusside, which was administered 1, 3, 6, 8, 24 hours after administering DA-8159. DA-8159 was absorbed rapidly with a Tmax of 0.6 hours in 30mg/kg and 1.0 hour in the 10mg/kg group, and T 1/2 of 1.23 hours in 30mg/kg and 1.17 hours in 10mg/kg, respectively. DA-8159 was not detected in the blood plasma 3 hours (10mg/kg) or 6 hours (30mg/kg) after administration. In an erection test, DA-8159 alone (10mg/kg) induced a penile erection for approximately 2 hours but there was no significant erection thereafter. Although the DA-8159-induced penile erection disappeared, an intravenous injection of sodium nitroprusside significantly induced a penile erection for 6 hours, when the plasma drug concentration was below the detection limit and a no longer visible erection was noted. These results demonstrate that DA-8159 is absorbed and rapidly cleared in rabbits. In addition, it can enhance a sodium nitroprusside-induced penile erection even after 6 hours, which is approximately five times longer than the plasma half-life in the rabbits. These results suggest that DA-8159 may have an erectile potential for much longer than its measured half-life.

DA-8159 has erectile potentials much longer than the plasma half-life in a conscious rabbit model

DA-8159 is a pyrazolopyrimidinone derivative which is a potent and selective phosphodiesterase type 5 inhibitor. The efficacy of oral DA-8159 has been demonstrated in conscious and spinalized rabbits by its enhancement of nitric oxide-induced erections. The aim of this study was to investigate the time dependency of this efficacy on its plasma concentration in rabbits. DA-8159 was given orally to normal rabbits at a dose of 10 or 30mg/kg in order to determine its pharmacokinetic parameters. After then, to investigate the relationship between penile erectile activity and plasma half-life, a dose of 10mg/kg DA-8159 was administered and the erectile response was examined in a time-course manner by measuring the length of the uncovered penile mucosa after the intravenous administration of sodium nitroprusside, which was administered 1, 3, 6, 8, 24 hours after administering DA-8159. DA-8159 was absorbed rapidly with a Tmax of 0.6 hours in 30mg/kg and 1.0 hour in the 10mg/kg group, and T1/2 of 1.23 hours in 30mg/kg and 1.17 hours in 10mg/kg, respectively. DA-8159 was not detected in the blood plasma 3 hours (10mg/kg) or 6 hours (30mg/kg) after administration. In an erection test, DA-8159 alone (10mg/kg) induced a penile erection for approximately 2 hours but there was no significant erection thereafter. Although the DA-8159-induced penile erection disappeared, an intravenous injection of sodium nitroprusside significantly induced a penile erection for 6 hours, when the plasma drug concentration was below the detection limit and a no longer visible erection was noted. These results demonstrate that DA-8159 is absorbed and rapidly cleared in rabbits. In addition, it can enhance a sodium nitroprusside-induced penile erection even after 6 hours, which is approximately five times longer than the plasma half-life in the rabbits. These results suggest that DA-8159 may have an erectile potential for much longer than its measured half-life.

Efficacy of DA-8159, a new PDE5 inhibitor, for inducing penile erection in rabbits with acute spinal cord injury.

DA-8159 is a pyrazolopyrimidinone derivative which exhibits potent and selective phosphodiesterase type 5 (PDE5) inhibition. The aim of this study was to investigate the effects of DA-8159 on inducing a penile erection in rabbits with an acute spinal cord injury (ASCI). DA-8159 was given either orally (1, 3, or 10 mg/kg) or intravenously (0.1 or 0.3 mg/kg) to conscious male albino rabbits with a surgical transection of the spinal cord at the L2-L4 lumbar vertebra or ischemic-reperfusion SCI rabbits. Erection was evaluated in a time-course manner by measuring the length of the uncovered penile mucosa. DA-8159 induced a dose-dependent erection in both transection and ischemic-reperfusion ASCI rabbits. The efficacy of DA-8159 was potentiated by an intravenous injection of sodium nitroprusside, a nitric oxide donor. Potentiation of the effect by nitric oxide donor implies that DA-8159 can enhance the erectile activity during sexual arousal. These results suggest that DA-8159 may be useful for treating erectile dysfunction in patients with an SCI.

DA-8159, a new PDE5 Iihibitor, induces penile erection in conscious and acute spinal cord injured rabbits.

DA-8159 is a pyrazolopyrimidinone derivative showing potent and selective phosphodiesterase 5 (PDE5) inhibition. In the previous study, DA-8159 induced a dose-dependent increase in the intracavernous pressure (ICP) in anaesthetized dogs. The aim of this study was to investigate the effects of DA-8159 on penile erection in conscious and acute spinal cord injured (ASCI) rabbits. DA-8159 was given orally (0.3 to 10mg/kg) to normal rabbits and ASCI rabbits with a surgical transection of the spinal cord at the L2-L4 lumbar vertebra or ischemic-reperfusion. The erection was evaluated in a time-course manner by measuring the length of the uncovered penile mucosa in the absence or presence of intravenous sodium nitroprusside (SNP), a nitric oxide (NO) donor. DA-8159 induced a dose-dependent penile erection in both the conscious and ASCI rabbits. The efficacy of DA-8159 was potentiated and the effective doses were significantly decreased by an intravenous injection of SNP. Potentiation of the effect by a nitric oxide donor implies that DA-8159 can enhance the erectile activity during sexual arousal. These results demonstrate that DA-8159 may be a useful treatment option for erectile dysfunction in patients with or without a spinal cord injury, but further evaluation of the effects of DA-8159 on humans must be performed.

Responses of neurons in the insular cortex to gustatory, visceral, and nociceptive stimuli in rats.

Extracellular unit responses to baroreceptor and chemoreceptor stimulation, gustatory stimulation of the posterior tongue, electrical stimulation of the superior laryngeal (SL) nerve, and tail pinch were recorded from the insular cortex of anesthetized and paralyzed rats. Forty-three neurons identified responded to stimulation by at least one of the stimuli used in the present study. Of the 43 neurons, 33 responded to tail pinch, and the remaining 10 had no response; 18 showed an excitatory response, and 15 showed an inhibitory response. Of the 43 neurons, 35 responded to electrical stimulation of the SL nerve; 27 showed an excitatory response, and 8 showed an inhibitory response. Of the 20 neurons that responded to baroreceptor stimulation by an intravenous injection of methoxamine hydrochloride (Mex), 11 were excitatory and 9 were inhibitory. Twenty-seven neurons were responsive to an intravenous injection of sodium nitroprusside (SNP); 10 were excitatory and 17 were inhibitory. Ten neurons were excited and 16 neurons were inhibited by arterial chemoreceptor stimulation by an intravenous injection of sodium cyanide (NaCN). Twenty-six neurons were responsive to at least one of the gustatory stimuli (1.0 M NaCl, 30 mM HCl, 30 mM quinine HCl, and 1.0 M sucrose): four to six excitatory neurons and three to nine inhibitory neurons for each stimulus. A large number of the neurons (42/43) received convergent inputs from more than one stimulus among the nine stimuli used in the present study. Most neurons (38/43) were responsive to two or more stimulus groups when the natural stimuli used in the present study are grouped into three, gustatory, visceral, and nociceptive stimuli. The neurons recorded were located in the insular cortex between 2.8 mm anterior and 1.1 mm posterior to the anterior edge of the joining of the anterior commissure (AC); the mean location was 1.0 mm (n = 43) anterior to the AC. This indicates that most of the neurons identified in the present study were located in the region posterior to the taste area and anterior to the visceral area in the insular cortex. These results indicate that the insular cortex neurons distributing between the taste area and the visceral area receive convergent inputs from baroreceptor, chemoreceptor, gustatory, and nociceptive organs and may have roles in taste aversion or in regulation of visceral responses.

Cardiovascular and neurohormonal effects of intravenous adrenomedullin in conscious rabbits.

Adrenomedullin is a vasodilative peptide and shows slight homology with calcitonin gene-related peptide. In the present study, we investigated the effects of adrenomedullin on cardiovascular and neurohormonal responses in 13 conscious rabbits. The animals were chronically instrumented with bipolar electrodes on the left renal sympathetic nerve. Intravenous administration of human adrenomedullin (10, 100, 1,000, and 3,000 pmol/kg, n = 6) caused a dose-dependent reduction in mean arterial pressure (0 +/- 2, -1 +/- 2, -19 +/- 2, and -29 +/- 4 mmHg, respectively) concomitant with increases in heart rate, renal sympathetic nerve activity, plasma renin activity, and plasma norepinephrine. The significant reduction in mean arterial pressure induced by 1,000 pmol/kg of adrenomedullin occurred within 1 min after injection and lasted for 15 min (n = 7). In contrast, the significant increases in heart rate and renal sympathetic nerve activity lasted for more than 50 min. When mean arterial pressure was decreased by 15 mmHg by adrenomedullin, the increases in heart rate and renal sympathetic nerve activity were 53 +/- 8 beats/min and 78 +/- 13%, respectively, which were significantly smaller than those induced by intravenous injection of sodium nitroprusside (102 +/- 14 beats/min and 155 +/- 34%, respectively). These results suggest that intravenous adrenomedullin exerts a hypotensive action that is associated with the attenuated reflex-mediated sympathetic activation.

Gonadotropin-stimulated regulation of blood-follicle barrier is mediated by nitric oxide

Although initially described over 30 years ago, the blood-follicle barrier has remained a biological enigma. In this study, we characterize the blood-follicle barrier with respect to its regulation of intrafollicular inter-alpha-trypsin inhibitor protein (I alpha I) influx after an ovulatory stimulus. We have found that I alpha I is localized within the ovarian vasculature but is excluded from the follicular compartment until an ovulatory stimulus is given. Within minutes after an ovulatory dose of human chorionic gonadotropin, I alpha I is localized within the follicular fluid of responding follicles where this protein becomes associated with and stabilizes the newly synthesized hyaluronic acid-rich cumulus extracellular matrix. Analysis of this process has shown that intravenous injection of sodium nitroprusside or excess substrate for nitric oxide synthase, L-arginine, mimics the effect of gonadotropic hormones on the influx of I alpha I into the follicular compartment of preovulatory follicles. Moreover, intravenous injection of specific nitric oxide synthase inhibitors, NG-nitro-L-arginine methyl ester and NG-nitro-L-arginine, inhibits gonadotropin-mediated intrafollicular influx of I alpha I and also inhibits ovulation in the mouse.

In Vivo Spin Trapping of Nitric Oxide in Mice

We report here an in vivo spin-trapping technique combined with electron paramagnetic resonance (EPR) spectroscopy to measure nitric oxide (·NO) production in the blood circulation of conscious mice. The method is based on the trapping of nitric oxide (·NO) by a metal-chelator complex consisting of N-methyl-D-glucamine dithiocarbamate (MGD) and reduced iron (Fe2+) to form a stable and water-soluble [(MGD)2-Fe2+-NO] complex, which gives rise to a characteristic three-line EPR spectrum of a mononitrosyl-Fe2+ complex (aN= 12.5 G and giso=2.04) at ambient temperatures. After simultaneous intravenous injection of sodium nitroprusside (an ·NO donor) and the [(MGD)2-Fe2+] complex into the lateral vein of the mouse tail, the appearance of the three-line spectrum in the blood circulation of the mouse tail was monitored continuously by using an S-band EPR spectrometer, operating at 3.5 GHz. This represents the first spin trapping of ·NO in living animals.

Intracellular analysis in vivo of different barosensitive bulbospinal neurons in the rat rostral ventrolateral medulla

Neurons located in the rostral ventrolateral medulla (RVLM) with projections to the intermediolateral column (IML) in the spinal cord were electrophysiologically characterized and anatomically identified using an intracellular recording technique in vivo. A group of spontaneously active neurons was antidromically activated by electrical stimulation of the IML in the thoracic spinal cord (T2-T3 level). The axonal conduction velocities ranged from 1.5 m/sec to 11.0 m/sec; mean value, 5.5 +/- 2.6 m/sec (+/- SD). The firing pattern and changes in membrane potential in relation to the cardiac cycle were investigated in these bulbospinal neurons. A first group discharged action potentials with higher frequency at the end of the diastolic/beginning of the systolic period. The average of the neuronal membrane potentials demonstrated depolarizing potentials at the end of the diastolic/beginning of the systolic period. These depolarizing potentials increased in magnitude when the neurons were hyperpolarized. Therefore, they were characterized as EPSPs. The baroreceptor reflex activation produced by the increase in systemic arterial pressure following intravenous injection of phenylephrine elicited hyperpolarization, a decrease in the rate of discharge, and an increase in the membrane input resistance, suggesting that a disfacilitatory effect was produced by the activation of baroreceptor inputs on these bulbospinal neurons. Conversely, the inactivation of the baroreceptor reflex by intravenous injection of sodium nitroprusside produced depolarization and an increase in the firing rate. These neurons were characterized as baroreceptor-sensitive type I neurons. A second group of bulbospinal neuron in the RVLM was differentiated from the first group because it demonstrated a decrease in the frequency of discharge at the end of the diastolic/beginning of the systolic period. The average of the membrane potentials showed hyperpolarizing potentials that decreased in magnitude when the neuron was hyperpolarized. These hyperpolarizing potentials occurred at the end of the diastolic/beginning of the systolic period and were reversed in polarity after intracellular injections of chloride ions for several minutes. Therefore, these potentials were characterized as chloride-dependent IPSPs locked to the cardiac cycle. In some of these neurons, the electrical stimulation of the IML produced, in addition to the antidromic action potential, a monosynaptic EPSP with a shorter latency. Based on these unique characteristics, these neurons were defined as barosensitive type II neurons. During constant baroreceptor inactivation achieved by the hypotension produced by intravenous infusions of sodium nitroprusside, the pattern of discharge of barosensitive type II neurons became very regular, and the IPSPs locked to the cardiac cycle were absent.(ABSTRACT TRUNCATED AT 400 WORDS)

Inhibitory effect of renal nerve activity during canine anaphylactic hypotension

We have examined baroreceptor regulation of renal nerve activity (RNA) during anaphylactic hypotension that affects renal nerve activity. In anesthetized dogs, mean blood pressure (MBP), heart rate (HR), and RNA were simultaneously measured. To test for a normally functioning baroreceptor reflex in each animal, a transient hypotension was induced by an intravenous injection of sodium nitroprusside (4 micrograms/kg). Nitroprusside produced a reflex increase in RNA (+63 +/- 12% at -20 mmHg and +139 +/- 8% at -40 mmHg) and HR (+13 +/- 1 beats/min at -20 mmHg and +21 +/- 2 beats/min at -40 mmHg). However, intravenous administration of Ascaris suum antigen in animals with an intact neuraxis caused a decrease in RNA (-15 +/- 14% at -20 mmHg and -42 +/- 11% at -40 mmHg blood pressure during the antigen-induced hypotension) in parallel with a fall in systemic blood pressure. HR responses were -5 +/- 2 beats/min at -20 mmHg and -10 +/- 1 beats/min at -40 mmHg during the hypotension induced by the antigen. In animals with combined denervation of the carotid sinus and vagal nerves, HR did not change significantly during anaphylactic hypotension. However, a decrease in RNA remained (-60 +/- 4% at -20 mmHg and -72 +/- 4% at -40 mmHg of hypotension). The decrease in RNA after antigen administration was significantly greater after denervation than in animals with an intact neuraxis. These results indicate that systemic baroreceptor reflex control of RNA is reduced during anaphylactic hypotension. Impaired reflex control of sympathetic nerve activity may result from an impairment of sympathetic outflow through the central nervous system.

Changes in the arterial blood pressure increase the release of endogenous histamine in the hypothalamus of anaesthetized cats.

The posterior hypothalamus of anaesthetized cats was superfused with artificial CSF through a push-pull cannula and the arterial blood pressure was recorded in the femoral artery. The release of endogenous histamine was determined in the hypothalamic superfusate by a radioenzymatic assay. Intravenous injection of sodium nitroprusside elicited a fall of blood pressure which was accompanied by an increase in the rate of release of endogenous histamine in the posterior hypothalamus. Similary, a controlled bleeding lowered the arterial blood pressure and enhanced the release of histamine. The durations of depressor responses to nitroprusside or controlled bleeding coincided with the duration of the changes in the rate of release of histamine. Intravenous injection of chlorisondamine also lowered the arterial blood pressure and augmented the release of histamine. However, the hypotension lasted longer than the increased release of histamine in the hypothalamus.

Modification of the baroreceptor reflex by superfusion of the canine posterior hypothalamus with tetrodotoxin.

The role of the posterior hypothalamus in the baroreceptor reflex was investigated in dogs. The posterior hypothalamus was superfused bilaterally through push-pull cannulae with artificial cerebrospinal fluid. After bilateral superfusion with tetrodotoxin (10(-5) M) for 120 min, the increases in mean arterial pressure and heart rate induced by the electrical stimulation of the posterior hypothalamus were almost abolished, and the resting mean arterial pressure was significantly decreased. Under these circumstances the increases in mean arterial pressure and heart rate in response to bilateral carotid occlusion were significantly reduced. The decrease in mean arterial pressure induced by intravenous injection of sodium nitroprusside (5 micrograms/kg) was significantly augmented while the associated increase in heart rate was suppressed. These results suggest that the posterior hypothalamus plays an important role in maintaining the resting arterial pressure and in the baroreceptor reflex to increase the arterial pressure and heart rate.

Attenuation of Blood Pressure Response to Laryngoscopy and Tracheal Intubation with Sodium Nitroprusside

The time course and magnitude of change in mean arterial pressure (MAP) and heart rate (HR) following a single rapid intravenous injection of 1 fig/kg and 2μg/kg of sodium nitroprusside (SNP) were determined in six anesthetized patients in the absence of concurrent stimulation produced by laryngoscopy or surgery. These data indicated that SNP administered 15 seconds before starting laryngoscopy would match the blood pressure lowering effects of SNP with the increase in blood pressure produced by laryngoscopy and tracheal intubation. The change in MAP and HR during and after laryngoscopy for tracheal intubation was determined in patients receiving 1 μg/kg (10 patients) or 2 μg/kg (10 patients) of SNP 15 seconds before starting laryngoscopy. These data were compared with data for 10 patients not receiving SNP. All patients studied were scheduled for elective saphenous vein to coronary artery bypass graft operations. Immediately after tracheal intubation the maximum increase in MAP above awake levels was 18 torr (p 0.05) whereas the increase without SNP was significantly greater (p A single rapid intravenous injection of SNP (1 to 2 μg/kg) is a practical pharmacologic method to attenuate blood pressure increases during direct laryngoscopy and tracheal intubation. Prevention of hypertension during the sequence surrounding tracheal intubation is particularly important in patients with decreased myocardial reserve or intracranial pathology.