Biomedical subjects

K G Cornish

Publications and source records attributed to K G Cornish.

At least 19 recordsLinked to original sources

PubMed2003

Amelioration of depressed cardiopulmonary reflex control of sympathetic nerve activity by short-term exercise training in male rabbits with heart failure.

The reflex regulation of sympathetic nerve activity has been demonstrated to be impaired in the chronic heart failure (CHF) state compared with the normal condition (Liu JL, Murakami H, and Zucker IH. Circ Res 82: 496-502, 1998). Exercise training (Ex) appears to be beneficial to patients with CHF and has been shown to reduce sympathetic outflow in this disease state (Hambrecht R, Hilbrich L, Erbs S, Gielen S, Fiehn E, Schoene N, and Schuler G. J Am Coll Cardiol 35: 706-713, 2000). We tested the hypothesis that Ex corrects the reduced cardiopulmonary (CP) reflex response to volume expansion in the CHF state. Normal, normal with Ex, CHF, and CHF with Ex (CHF-Ex) groups (n = 10-21) of male New Zealand White rabbits were studied. CHF was induced by chronic ventricular pacing. Rabbits were instrumented to record left ventricular end-diastolic pressure (LVEDP), left ventricular end-diastolic diameter (LVEDD), and renal sympathetic nerve activity (RSNA). Experiments were carried out with the animals in the conscious state. Volume expansion was performed with 6% dextran in normal saline at a rate of 5 ml/min to approximately 20% of estimated plasma volume without any significant effect on mean arterial pressure being exhibited. The relationships between RSNA and LVEDP and between RSNA and LVEDD were determined by linear regression; the slopes served as an index of CP reflex sensitivity. Normal rabbits exhibited a CP reflex sensitivity of -8.4 +/- 1.5%delta RSNA/mmHg. This value fell to 0.0 +/- 1.3%delta RSNA/mmHg in CHF rabbits (P < 0.001). Ex increased CP reflex sensitivity to -5.0 +/- 0.7%delta RSNA/mmHg in CHF-Ex rabbits (P < 0.05 compared with CHF). A similar trend was seen when related to the change in LVEDD. Furthermore, resting RSNA expressed as a percentage of maximum RSNA in response to cigarette smoke was also normalized by Ex in rabbits with CHF. Ex had no effect on these parameters in normal rabbits. These data confirm an impairment of CP reflex sensitivity and sympathoexcitation in CHF vs. normal animals. Ex substantially restored both CP reflex sensitivity and baseline RSNA in CHF animals. Thus Ex beneficially affects reflex regulation in CHF, thereby lowering resting sympathetic nerve activity.

Animals↗

PubMed2001

Chronic endothelin-1 blockade reduces sympathetic nerve activity in rabbits with heart failure.

Endothelin-1 (ET-1) is elevated in chronic heart failure (CHF). In this study, we determined the effects of chronic ET-1 blockade on renal sympathetic nerve activity (RSNA) in conscious rabbits with pacing-induced CHF. Rabbits were chronically paced at 320--340 beats/min for 3--4 wk until clinical and hemodynamic signs of CHF were present. Resting RSNA and arterial baroreflex control of RSNA were determined. Responses were determined before and after the ET-1 antagonist L-754,142 (a combined ET(A) and ET(B) receptor antagonist, n = 5) was administered by osmotic minipump infusion (0.5 mg. kg(-1) x h(-1) for 48 h). In addition, five rabbits with CHF were treated with the specific ET(A) receptor antagonist BQ-123. Baseline RSNA (expressed as a percentage of the maximum nerve activity during sodium nitroprusside infusion) was significantly higher (58.3 +/- 4.9 vs. 27.0 +/- 1.0, P < 0.001), whereas baroreflex sensitivity was significantly lower in rabbits with CHF compared with control (3.09 +/- 0.19 vs. 6.04 +/- 0.73, P < 0.001). L-754,142 caused a time-dependent reduction in arterial pressure and RSNA in rabbits with CHF. In addition, BQ-123 caused a reduction in resting RSNA. For both compounds, RSNA returned to near control levels 24 h after removal of the minipump. These data suggest that ET-1 contributes to sympathoexcitation in the CHF state. Enhancement of arterial baroreflex sensitivity may further contribute to sympathoinhibition after ET-1 blockade in heart failure.

Acetamides↗

PubMed1999

Bolus intravenous injection of phosphorothioate oligonucleotides causes hypotension by acting as alpha(1)-adrenergic receptor antagonists.

Bolus intravenous injections of phosphorothioate oligonucleotides (PS-ODN) into primates cause profound hypotension, which has been attributed to complement activation, the biochemical pathway leading to acute inflammatory response. Because the hypotension was not accompanied by peripheral or pulmonary edema and epinephrine was not effective, but administration of 200 ml Ringer's lactate was effective, we examined the possibility that the 15-base PS-ODN interferes with sympathetic tone. We administered doses ranging from 3.3 to 10 mg/kg of a 15-base PS-ODN as a 30-60 s iv bolus into the right atrium of conscious Macaca mulatta. Blood pressure fell to 27 mm Hg following a 5.0 mg/kg dose, but no hypotension was observed after a 3.3 mg/kg dose; 10 mg/kg was lethal. Adrenergic receptor binding was evaluated in radioligand binding assays using rat cerebral cortex membranes with radiolabeled prazosin. The 15-base PS-ODN competes with prazosin for the alpha(1)-adrenergic receptor with an IC50 of 14 microM, which favors binding over serum albumin (K(d) = 37 to 48 microM). Admixing serum albumin with 5.0 mg/kg 15-base PS-ODN prior to injection prevented hypotension, suggesting that unbound PS-ODN interferes with sympathetic tone before binding to plasma proteins. Interactions of the 15-base PS-ODN with the alpha(1)-adrenergic receptor in vivo were confirmed by a decreased response to phenylephrine. Reducing the length from 15 to 9 or 5 bases abolished alpha(1)-adrenergic receptor binding in vitro and bolus infusion of 5.0 mg/kg of 9-base PS-ODN no longer produced hypotension. In conclusion, the 15-base PS-ODN shows cooperative binding to the alpha(1)-adrenergic receptor, which produces cardiovascular effects that are oligomer length, dose, and formulation dependent.

Adrenergic alpha-1 Receptor Antagonists↗

PubMed1999

Suppressed impact of nitric oxide on renal arteriolar function in rats with chronic heart failure.

We performed experiments to test the hypothesis that experimental heart failure (HF) is associated with altered nitric oxide (NO)-dependent influences on the renal microvasculature, including diminished modulation of constrictor responses to ANG II. Eight to ten weeks after inducing HF in rats by coronary artery ligation, we administered enalaprilat to suppress ANG II synthesis and studied renal arteriolar function using the in vitro blood-perfused juxtamedullary nephron technique. In kidneys from sham-operated rats, NO synthase inhibition [100 microM Nomega-nitro-L-arginine (L-NNA)] reduced afferent arteriolar diameter by 4.1 +/- 0.6 microm and enhanced ANG II responsiveness (10 nM ANG II decreased afferent diameter by 10.1 +/- 1.4 micrometer before and 12.8 +/- 1.6 micrometer during L-NNA treatment; P < 0.05). In kidneys from HF rats, L-NNA did not alter afferent arteriolar baseline diameter or ANG II responsiveness (10 nM ANG II decreased diameter by 12.5 +/- 1.5 micrometer before and 12.5 +/- 2.3 micrometer during L-NNA). The effects of L-NNA on efferent arteriolar function were also abated in HF rats. In renal cortex of HF rats, NO synthase activity was decreased by 63% and superoxide dismutase activity was diminished by 39% relative to tissue from sham-operated rats. Urinary nitrate/nitrite excretion was also reduced in HF rats. Thus both diminished synthesis and augmented degradation are likely to contribute to a decreased renal microvascular impact of endogenous NO during chronic HF, the consequences of which include loss of NO-dependent modulation of ANG II-induced vasoconstriction.

Animals↗

PubMed1999

Head-out immersion in the non-human primate: a model of cardiovascular deconditioning during microgravity.

BACKGROUND: Orthostatic intolerance is a common complication associated with spaceflight. It has been speculated that this is due to changes in blood volume and alterations in cardiovascular reflexes. The objective of the current study was to develop a model that would allow us to study the cardiovascular system and the regulation of blood volume during short-term microgravity exposure in the primate with the intent of eventually being able to elucidate those factors responsible for the orthostatic intolerance. HYPOTHESIS: Head-out water immersion in the conscious non-human primate simulates the cardiovascular and volume regulatory responses observed in astronauts during exposure to microgravity. METHODS: Four monkeys were chronically instrumented for measuring BP and heart rate and then conditioned to the primate restraint chair. They were then subjected to 72 h of head-out water immersion (two immersions in three monkeys and one immersion in the fourth) in order to simulate the cardiovascular and renal effects of the microgravity environment. RESULTS: During the immersion, there was an increase in arterial BP (ABP) and central venous pressure (CVP) and a reflex decrease in heart rate (HR). Urine flow (UV) increased and water intake decreased, producing a negative water balance. This was not associated with an alteration in food intake. CVP and UV decreased following de-immersion. There was also resetting of the arterial baroreflex control of HR. Significant tachycardia occurred after the immersion that was associated with a decrease in ABP. CONCLUSION: These results are similar to those observed in astronauts during and after spaceflight, suggesting that head-out water immersion of the non-human primate provides a good model for studying cardiovascular and renal adaptations to spaceflight.

Animals↗

PubMed1998

Synthesis and biological evaluation of [11C]MK-912 as an alpha2-adrenergic receptor radioligand for PET studies.

In vitro studies showed that MK-912 ((2S, 12bS)1',3'-dimethylspiro(1,3,4,5',6,6',7,12b-octahydro -2H-benzo[b]furo[2,3-a]quinolizine)-2,4'-pyrimidin-2'-one) is a potent alpha2-adrenergic receptor antagonist with high affinity (Ki = 0.42, 0.26 and 0.03 nM to alpha2A, alpha2B and alpha2C, respectively) and high selectivity (alpha2A/alpha1A = 240; alpha2A/D-1 = 3600; alpha2A/D-2 = 3500; alpha2A/5-HT1 = 700; alpha2A/5-HT2 = 4100). The compound was labeled with 11C and evaluated in rodents and monkey as a specific radioligand for studying alpha2-adrenergic receptors using PET. [11C]MK-912 was synthesized by methylation of its desmethyl precursor, L-668,929, with [11C]CH3I in (Bu3O)P=O at 85 degrees C for 8 min followed by purification with HPLC in 18% yield in a synthesis time of 45 min from end of bombardment (EOB). The specific activity was 0.83-0.93 Ci/micromol and the radiochemical purity was 97%. The initial uptake of [11C]MK-912 in mouse brain, heart, lung, liver and kidney was high (5%, 4%, 5%, 17% and 8% per gram of organ, respectively, at 5 min postinjection) and the activities were then slowly cleared from these organs. The uptake of [11C]MK-912 in rat olfactory tubercle, a brain region with high density of alpha2-adrenergic receptors, was reduced by 30%, and the ratio of radioactivity in olfactory tubercle/cerebellum was reduced from 2:1 to 1:1 by coinjection of [11C]MK-912 with a potent alpha2-adrenergic receptor antagonist, atipamezole (3 mg/kg), indicating that compound 2 binds to alpha2-adrenergic receptors. However, a PET study in a rhesus monkey revealed that the initial influx of [11C]MK-912 into various brain regions (cerebellum, cortex, olfactory tubercle and striatum) was high (0.02%/cc), and the radioactivity was then washed out slowly and without significantly differential retention in these brain regions. This, coupled with the fact that none of the high-density alpha2-adrenergic receptor brain regions exceeds a few millimeters in diameter, suggests that [11C]MK-912 is probably not an ideal radioligand for studying alpha2-adrenergic receptors in humans using commercially available PET.

Adrenergic alpha-Antagonists↗

PubMed1995

Comparative PET studies of the distribution of (-)-3,4-methylenedioxy-N-[11C]methamphetamine and (-)-[11C]methamphetamine in a monkey brain.

Carbon-11 labeled (-)-methamphetamine and (-)-3,4-methylenedioxy-N-methamphetamine were synthesized by methylation of the corresponding desmethyl precursors with [11C]H3I in 40-60% yield in a synthesis time of 30 min from EOB with a specific activity of 0.5-1.2 Ci/microM. PET studies in a Rhesus monkey revealed that the uptakes of both compounds in different brain regions were similar, and the retention of radioactivity in these brain regions remained constant throughout the study for the former while it was washed out slowly for the latter. The half-life of (-)-3,4-methylenedioxy-N-methamphetamine in monkey brain was approximately 70 min. Analyses of arterial plasma by HPLC revealed that 50% of radioactivity in the plasma remained as (-)-methamphetamine while only 3% remained as (-)-3,4-methylenedioxy-N-methamphetamine at 60 min post-injection. These results suggest that the uptakes of both compounds in monkey brain are probably not receptor mediated. Rather, blood flow, lipophilicity of the compounds or other transport mechanisms may play a role in their uptakes.

3,4-Methylenedioxyamphetamine↗

PubMed1995

PET study of the distribution of [11C]fluoxetine in a monkey brain.

No-carrier-added [11C]fluoxetine (2) was synthesized by methylation of norfluoxetine (1) with [11C]H3I in 20% radiochemical yield in a synthesis time of 40 min from EOB with a specific activity of 0.48 Ci/microM (EOB). In vivo study in mouse indicated that the uptake of 2 in mouse tissues was high and the radioactivity remained constant throughout the study. The uptake of 2 in mouse brain was 4%/g. PET study in a Rhesus monkey also showed that the uptakes of 2 in different brain regions were similar and the retention of radioactivity in these regions remained constant throughout the study (80 min). Analysis of arterial plasma by HPLC showed that only 20% of radioactivity in the plasma remained as 2 at 30 min post-injection. These results suggest that the uptake of fluoxetine in monkey brain is probably not receptor mediated. Rather, blood flow, lipophilicity or other transport mechanisms may play a role in its uptake.

Animals↗

PubMed1994

Sequence of a cDNA encoding the p53 protein in rhesus monkey (Macaca mulatta).

A 2184-nucleotide (nt) sequence of the p53 gene in Rhesus monkey (Macaca mulatta) was determined in order to facilitate the use of the Rhesus as an animal model in the testing of novel antisense oligodeoxyribonucleotides for a variety of human cancers, including acute myelogenous leukemia (AML). Within overlapping regions, we found greater than 95% identity between the Rhesus and human p53 sequences, and greater than 98% identity between Rhesus and African green monkey p53 sequences. The deduced amino acid (aa) sequence of the p53 protein is highly conserved between human and Rhesus monkey, with only 18 minor differences in 393 aa.

Amino Acid Sequence↗

PubMed1993

Fluorine-18 and carbon-11 labeled amphetamine analogs--synthesis, distribution, binding characteristics in mice and rats and a PET study in monkey.

No-carrier-added (NCA) (+-)-p-[18F]fluoroamphetamine (2a) and (+-)-6-[18F]fluoro-3,4-methylene-dioxy-amphetamine (2b) were synthesized through a multistep synthesis by nucleophilic substitution of the appropriate precursors (p-nitrobenzaldehyde, 1a and 6-nitropiperonal 1b, respectively) with [18F]fluoride followed by condensation with nitroethane and reduction with LAH in 20-30% yield (EOB) in a synthesis time of 90-109 min from EOB. NCA (-)-[11C]methamphetamine (4a) and (+-)-3,4-methylene-dioxy-N-[11C]methamphetamine (4b) were synthesized by methylation of the appropriate desmethyl precursors 3a and 3b with [11C]H3I in 40-60% yield (EOB) in a synthesis time of 30 min from EOB. Animal studies in mouse and rat revealed that the relative tissue uptake of these radiotracers was kidneys > lungs > liver > spleen > brain > heart > blood. The uptakes of these radiotracers in mouse brain were high and similar at 5 min post-injection (approx. 5%/g) but radioactivity then declined rapidly (approx. 1%/g at 60 min post-injection). For compounds 2a and 2b, the activity in the femur did not increase with time indicating in vivo defluorination may not be the major route of metabolism. Monoamine uptake inhibitors (nomifensine, fluoxetine and nisoxetine) did not inhibit but enhance the uptake of (-)-[11C]methamphetamine (4a) in the rat brain by greater than 50%. A PET study in a Rhesus monkey revealed that the uptakes of (-)-[11C]methamphetamine in different brain regions were similar and the retention of the radioactivity in these regions remained constant throughout the study. Analysis of arterial plasma by HPLC showed that 50% of radioactivity remained as 4a at 60 min post-injection.

Amphetamines↗

PubMed1992

Intracoronary veratrine attenuates carotid baroreceptor reflex regulation of blood pressure in conscious dogs.

1. The effect of activation of left ventricular cardiac receptors on carotid baroreflex control of blood pressure, heart rate, cardiac output, and total peripheral resistance was determined in conscious dogs. Previous studies in conscious subjects assessed only the effect on baroreflex control of heart rate. 2. Dogs with denervated aortic baroreceptors were equipped with aortic flow probes, cardiac pacing electrodes, and catheters in the aorta, vena cava, and left circumflex coronary artery. Both carotid sinus regions were prepared for reversible vascular isolation. 3. Left ventricular receptors were stimulated by an infusion of veratrine (0.1-1.0 micrograms kg-1 min-1) into the left circumflex coronary artery. 4. Veratrine infusion decreased control blood pressure only 10 +/- 2 mmHg, but it decreased the range of baroreflex control of blood pressure by 50% and decreased maximum baroreflex gain by 42%. Both the cardiac output and total peripheral resistance components of the baroreflex were attenuated. 5. Baroreflex control of blood pressure was unaffected by intravenous veratrine or by intracoronary infusion of vehicle. 6. Intracoronary veratrine had no effect after autonomic ganglionic blockade. 7. When cardiac output was kept nearly constant (by beta-adrenergic and cholinergic receptor blockade or by beta-blockade and cardiac pacing), intracoronary veratrine still attenuated baroreflex control of blood pressure and total peripheral resistance. Veratrine impaired the ability of the baroreflex to utilize alpha-adrenergic mechanisms to control total peripheral resistance. 8. We conclude that activation of ventricular receptors attenuates baroreflex regulation of blood pressure in conscious dogs through an attenuation of baroreflex control of both cardiac output and total peripheral resistance.

Animals↗

PubMed1992

Baro- and ventricular reflexes in conscious dogs subjected to chronic tachycardia.

It has been well documented that the arterial baroreflex is depressed in chronic congestive heart failure. Furthermore, cardiopulmonary reflexes have also been shown to be depressed in heart failure. Because cardiac reflexes can be mediated by both mechanical and chemical stimuli, we undertook the current study to determine whether chemically activated cardiac reflexes (Bezold-Jarisch) are abnormally depressed in dogs with chronic heart failure at a point in time when arterial baroreflexes were clearly depressed. We studied heart rate and arterial pressure responses in 13 conscious instrumented dogs before and after chronic ventricular pacing at 250 beats/min for 4-5 wk. At the time the study was done each dog showed both hemodynamic and clinical signs of congestive heart failure. The arterial baroreflex was evaluated by analyzing the heart rate response to acute injections of phenylephrine and nitroglycerin. The Bezold-Jarisch reflex was assessed in nine dogs by determining the heart rate and blood pressure responses to intracoronary injections of various doses of veratridine. Arterial baroreflex responses were uniformly depressed following ventricular pacing. The phenylephrine slope was reduced by 55.8 +/- 6.9% (P < 0.001), and the nitroglycerin slope was reduced by 67.9 +/- 5.0% (P < 0.0001) in the heart failure state. Significant bradycardia and hypotension were seen at each dose of veratridine given (0.01, 0.1, and 0.4 microgram/kg). When compared with the prepaced control state, the magnitude of the hypotension was no different in the heart failure state in response to any dose of veratridine.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1992

Synthesis and biodistribution of the alpha 2-adrenergic receptor antagonist (11C)WY26703. Use as a radioligand for positron emission tomography.

The purpose of these experiments was to label an alpha 2-adrenergic receptor ligand with a positron emitting isotope and then test this radioligand in vivo. No-carrier-added [11C]WY26703 was synthesized by methylation of its desmethyl precursor, WY27050 with [11C]H3I followed by purification with HPLC in 14% yield in a synthesis time of 35 min from EOB. Ki values for unlabeled WY26703, ranged from 0.52-1.55 nM in tissues that express a single alpha 2-adrenergic receptor subtype. Tail vein injections of [11C]WY26703 in mice revealed that the compound was distributed in the brain, heart, lungs, spleen, and kidneys. In the brains of rats treated with atipamezole, an alpha 2-adrenergic receptor antagonist, there was no decrease in [11C] accumulation indicating a lack of observable specific binding of the radioligand. When brain tissue was homogenized and filtered, however, atipamezole decreased [11C] activity by 53%. Therefore, [11C]WY26703 crosses the blood-brain barrier and specifically binds to alpha 2-adrenergic receptors with high affinity. Atipamezole treatment decreased only the area of the locus coeruleus [11C] value of the various regions of the brain. The affinity, however, of [11C]WY26703 does not appear to distinguish alpha 2-receptors from nonspecific binding sites. PET study of [11C]WY26703 in a Rhesus monkey showed that influx of [11C]WY26703 into the brain was high for the first few minutes but radioactivity then declined rapidly and did not retain in a specific brain region. This suggests that [11C]WY26703 may not be a useful ligand for imaging human alpha 2-adrenergic receptors by positron emission tomography.

Adrenergic beta-Antagonists↗

PubMed1990

Neural and hormonal control of blood pressure in conscious monkeys.

The contribution of the autonomic nervous system, angiotensin II (ANG II), and arginine vasopressin (AVP) to the control of blood pressure (BP) was examined in 12 chronically instrumented tethered monkeys. The vasopressin antagonist, [d(CH2)5AVP] (Manning Compound, MC), the ANG II antagonist, saralasin (SAR), and the ganglionic blocking drug, hexamethonium (Hx), were injected in a random sequence into the left atrium (LA) while BP and heart rate (HR) were monitored. When given as the first antagonist, MC caused a slight decrease in BP; SAR did not significantly decrease BP regardless of the sequence of administration, whereas Hx caused a consistent decrease in blood pressure of 35-50 mmHg. Seven (4 intact and 3 with renal denervation) additional animals were involved in hemorrhage experiments. Blood pressure was reduced to 50-60 mmHg by hemorrhage and then allowed to return spontaneously. Ten to 15 min after the end of the hemorrhage, MC was given. When blood pressure had stabilized, SAR was given. Blood pressure returned to 80-90 mmHg after the hemorrhage. MC did not affect the blood pressure recovery; however, saralasin reduced it to the post-hemorrhage levels. We would conclude that the sympathetic nervous system is the primary controlling mechanism for BP in the conscious primate, with AVP making a minor contribution. The release of renin would appear to be primarily under the control of the sympathetic nervous system.

Animals↗

PubMed1989

PGE2 and arachidonate inhibit the baroreflex in conscious dogs via cardiac receptors.

Prostaglandin (PG) I2 and PGE2 are known to stimulate left ventricular receptors with nonmyelinated vagal afferents. The present experiments were performed to determine the effects of intracoronary infusion of PGE2 (10-50 ng.kg-1.min-1) and arachidonic acid (50-100 micrograms.kg-1.min-1) on the baroreflex control of heart rate in conscious dogs. Dogs were anesthetized with pentobarbital sodium and were instrumented using sterile surgical techniques. After recovery, baroreflex pressure-heart rate curves were constructed by varying arterial pressure with partial occlusions of the descending aorta or inferior vena cava. Intracoronary infusion of PGE2 significantly inhibited the maximum heart rate achieved during unloading of baroreceptors, attenuated the heart rate range, and decreased the maximum slope of the baroreflex curve; PGE2 had no significant effect on the minimum heart rate during hypertension. Intravenous infusion of PGE2 did not cause significant baroreflex inhibition, and pericoronary nerve block in three dogs prevented the effects of intracoronary PGE2. Intracoronary infusion of arachidonic acid had effects on the baroreflex control of heart rate similar to those of PGE2. The effects of arachidonic acid infusion were prevented by cyclooxygenase blockade. Thus intracoronary PGE2 and arachidonic acid inhibit the baroreflex control of heart rate most likely via stimulation of left ventricular receptors with vagal C-fiber afferents. The effects of arachidonic acid were secondary to synthesis of prostaglandins.

Animals↗

PubMed1989

Vasopressin potentiates ventricular and arterial reflexes in the conscious nonhuman primate.

The effect of arginine vasopressin (AVP) on the arterial baroreflex control of heart rate (HR) was studied in intact and sinoaortic-denervated (SAD) conscious, unrestrained monkeys. A baroreflex curve for mean arterial blood pressure (MABP) and HR was determined before and during intravenous infusion of AVP (2-4 mU.kg-1.min-1) and after the AVP vascular antagonist "Manning compound" [( d(CH2)5Tyr(Me)]AVP, 40 micrograms/kg), while AVP infusion was kept running. The sensitivity (slope) of the arterial baroreflex, as well as the reflex bradycardia induced by high blood pressure, increased significantly during AVP and returned to the control level after Manning compound. The effect of AVP on the Bezold-Jarisch reflex (induced by stimulating left ventricular receptors with 4 micrograms/kg veratridine injected in the left atrium) was also studied. The cardiovascular responses to veratridine were examined before and during AVP and after administration of Manning compound together with AVP infusion. AVP significantly potentiated the hypotension and the bradycardia produced by veratridine, whereas Manning compound blunted this potentiation. The ventricular reflex in SAD monkeys was significantly greater than in intact monkeys. We conclude that, in the conscious nonhuman primate, AVP potentiates the sensitivity of the baroreflex control of HR as well as the Bezold-Jarisch reflex. The potentiation of the Bezold-Jarisch reflex by AVP in the SAD animals is consistent with a central action, since the baroreceptors and ventricular receptors both have connections in the nucleus tractus solitarius. However, it does not rule out the possibility of peripheral actions on receptors or end organs.

Animals↗

PubMed1989

Volume expansion attenuates baroreflex sensitivity in the conscious nonhuman primate.

We examined the effect of intravascular volume expansion (VE) on the arterial baroreflex control of pulse rate (PR) in conscious, chronically instrumented monkeys tethered in their cages. A total of five monkeys was studied after surgical implantation of catheters in the descending aorta, the left atrium, and the internal jugular vein. Mean arterial blood pressure (MABP)-PR stimulus response curves were constructed by decreasing and increasing blood pressure with nitroprusside and phenylephrine, respectively. The data were analyzed with a regression analysis that generated a sigmoid curve and the maximum sensitivity (slope) of the curve. The data were obtained before and after VE with an isotonic isoncotic dextran solution equal to 20% of the estimated blood volume. After VE, the MABP-PR curve shifted to the right at the high blood pressures, and there was a significant decrease in the maximum sensitivity from 5.65 +/- 1.44 for control to 2.14 +/- 0.63 after VE (P less than 0.05). We concluded that VE attenuates the baroreflex control of heart rate in the conscious nonhuman primate.

Animals↗

PubMed1988

Central blood volume and blood pressure in conscious primates.

Conscious intact (I) and sinoaortic-denervated monkeys (SAD) were studied to determine the extent to which high-pressure receptors contribute to the maintenance of arterial blood pressure (BP) when venous return is decreased by hemorrhage (H) or lower body negative pressure (LBNP). In the I animals, mean BP did not decrease significantly until 5% of the estimated blood volume (EBV) was removed, whereas, with sinoaortic denervation, mean BP decreased significantly when less than 2% of EBV was removed. Left atrial pressure (LAP) decreased similarly in both groups of animals. In the I group during LBNP, mean BP did not change significantly, whereas pulse pressure decreased significantly when LBNP was decreased to -5 cmH2O. In the SAD animals, mean BP decreased significantly at an LBNP of -2 cmH2O, and at -5 cmH2O mean BP declined from 134.1 +/- 4 to 102.7 +/- 7 mmHg. LAP decreased similarly in both groups of animals. The data support the view that a nonhypotensive reduction in venous return unloads arterial baroreceptors sufficiently to activate the arterial baroreflex, probably through reductions in pulse pressure. In addition, low-pressure receptors by themselves do not appear to contribute importantly to blood pressure maintenance when venous return is decreased by either LBNP or a nonhypotensive hemorrhage.

Animals↗