Reflex cardiovascular responses to chemoreceptor stimulation in conscious dogs with cardiac hypertrophy

Carotid chemoreceptor reflex activation (CCRA) has been previously shown to result in intense alpha-adrenergic peripheral vasoconstriction, a biphasic coronary vascular response characterized by an early vasodilation and a late alpha-adrenergic vasoconstriction, and a cholinergic increase in cardiac cycle length in normal conscious dogs. In the present study, we investigated the extent to which these reflex cardiovascular responses to CCRA are modified after the development of pressure-overload right ventricular (RV) hypertrophy induced by chronic (9-12 mo) pulmonary arterial stenosis. With heart rate constant and respiration allowed to vary spontaneously, the magnitude of the late CCRA-induced (intracarotid nicotine) increase (P less than 0.01) in right coronary resistance was markedly attenuated (P less than 0.01) in conscious dogs with RV hypertrophy [0.29 +/- 0.07 (SE) mmHg X ml-1 X min] compared with normal dogs (1.87 +/- 0.36). When respiration was controlled to eliminate pulmonary inflation reflex activation, the late CCRA-induced increase (P less than 0.01) in right coronary resistance was still found to be depressed (P less than 0.01) in the RV hypertrophy group (1.11 +/- 0.20 mmHg X ml-1 X min) compared with normal dogs (3.65 +/- 0.75). This late CCRA-induced right coronary vasoconstriction was not potentiated by beta-adrenergic receptor blockade but was abolished (P less than 0.01) by alpha-adrenergic receptor blockade. In contrast to the depressed right coronary vasoconstriction, the CCRA-induced alpha-adrenergic constriction (P less than 0.01) of the iliac arterial vascular bed was similar in both groups, and the cholinergic increase (P less than 0.01) in cardiac cycle length was enhanced (P less than 0.01) in the RV hypertrophy group compared with normal dogs.(ABSTRACT TRUNCATED AT 250 WORDS)

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Intracoronary alpha 2-adrenergic receptor blockade attenuates ischemia in conscious dogs during exercise.

Circulation Research ◽

10.1161/01.res.62.3.436 ◽

1988 ◽

Vol 62 (3) ◽

pp. 436-442 ◽

Cited By ~ 97

Author(s):

R Seitelberger ◽

B D Guth ◽

G Heusch ◽

J D Lee ◽

K Katayama ◽

...

Keyword(s):

Adrenergic Receptor ◽

Conscious Dogs ◽

Receptor Blockade ◽

Adrenergic Receptor Blockade

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Neurally mediated cardiac effects of forskolin in conscious dogs

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.1996.271.4.h1473 ◽

1996 ◽

Vol 271 (4) ◽

pp. H1473-H1482 ◽

Cited By ~ 2

Author(s):

M. Iwase ◽

Y. Ishikawa ◽

Y. T. Shen ◽

R. P. Shannon ◽

N. Sato ◽

...

Keyword(s):

Heart Rate ◽

Adenylyl Cyclase ◽

Adrenergic Receptor ◽

Left Ventricular ◽

Conscious Dogs ◽

Receptor Blockade ◽

Beta Adrenergic Receptor ◽

Beta Adrenergic ◽

Ganglionic Blockade ◽

Adrenergic Receptor Blockade

Because major cardiovascular disease states are characterized by defects in adenylyl cyclase regulation, it becomes important to understand the mechanisms by which adenylyl cyclase activators affect inotropy and chronotropy in intact conscious animals. Accordingly, we examined the inotropic and chronotropic responses to forskolin in 11 normal conscious, chronically instrumented dogs and 3 dogs with ventricular denervation (VD). Left ventricular first derivative of pressure (LV dP/dt) increased by 96 +/- 7%, P < 0.05, in response to forskolin (50 nmol.kg-1.min-1) in normal dogs and by significantly less, 52 +/- 14%, in VD dogs. Circulating norepinephrine (NE) levels increased similarly in both groups (from 226 +/- 18 to 389 +/- 33 pg/ml in normal dogs, from 177 +/- 23 to 329 +/- 71 pg/ml in VD dogs). In the presence of ganglionic blockade, the increase in LV dP/dt in response to forskolin was reduced (+62 +/- 4%) in normal dogs but was unchanged in VD dogs (+52 +/- 12%). Ganglionic blockade abolished the increase in circulating NE levels in both groups. Increases in heart rate in the presence of ganglionic blockade (+54 +/- 6 beats/min) were less than in the presence of atropine alone (+92 +/- 10 beats/min). Notably, the LV dP/dt and heart rate responses to forskolin were further attenuated by beta-adrenergic receptor blockade in the presence and absence of ganglionic blockade. Morphine also attenuated the increases in both LV dP/dt and plasma NE in response to forskolin. Increases in LV dP/dt in response to NKH-477 (30 micrograms/kg), a water-soluble forskolin derivative, were similar before and after ganglionic blockade (+63 +/- 8 and +51 +/- 10%, respectively). However, in vitro experiments in LV sarcolemmal membrane preparations demonstrated that stimulation of adenylyl cyclase by forskolin and NKH-477 was not affected by beta-adrenergic receptor blockade. These results indicate that in conscious dogs, inotropic and chronotropic effects of forskolin are not only due to direct activation of adenylyl cyclase, but the effects also are mediated by neural mechanisms and potentiated by the prevailing level of sympathetic tone.

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Splenic contraction-induced increases in arterial O2 reduce requirement for CBF in conscious dogs

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.1995.269.2.h491 ◽

1995 ◽

Vol 269 (2) ◽

pp. H491-H503 ◽

Cited By ~ 8

Author(s):

N. Sato ◽

Y. T. Shen ◽

K. Kiuchi ◽

R. P. Shannon ◽

S. F. Vatner

Keyword(s):

Adrenergic Receptor ◽

Conscious State ◽

Conscious Dogs ◽

Receptor Blockade ◽

Sympathomimetic Amines ◽

Blood Flows ◽

Before And After ◽

Myocardial O2 Consumption ◽

Consequent Increase ◽

Adrenergic Receptor Blockade

We investigated the extent to which sympathomimetic amines induced splenic contraction and associated increases in arterial O2 content (CaO2) and how these mechanisms affected control of the coronary circulation by sympathomimetic amines in conscious dogs. Blood hemoglobin (Hb) and CaO2 increased by 16 +/- 2 and 18 +/- 2%, respectively, during norepinephrine (NE, 0.8 micrograms.kg-1.min-1 iv) in the intact, conscious state after splenic contraction. Phenylephrine (PE) induced similar effects. After either alpha 1-adrenergic-receptor blockade or splenectomy, these effects were abolished. Isoproterenol (Iso) also decreased splenic thickness, which was abolished after ganglionic, alpha-, or beta 1/beta 2-adrenergic-receptor blockade. Direct infusions of NE and PE into the splenic artery decreased splenic thickness and increased Hb and CaO2, whereas Iso had no effect. After splenectomy, NE did not increase CaO2, but coronary blood flow (CBF) increased more (73 +/- 6%) vs. before splenectomy (49 +/- 7%) without any differences before and after splenectomy in the responses of pressures, contractility, and myocardial O2 consumption (MVO2). In contrast, renal, mesenteric, and iliac artery blood flows were not significantly different in response to sympathomimetic amines before and after splenectomy. These data indicate that sympathomimetic amines induced splenic contraction either directly or reflexly via alpha-adrenergic-receptor stimulation. The consequent increase in Hb and CaO2 allows for equivalent increases in MVO2, but at a smaller increase in CBF.

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Effect of adrenergic receptor blockade on plasma testosterone response to exercise in conscious dogs

Archives Internationales de Physiologie de Biochimie et de Biophysique ◽

10.3109/13813459409007537 ◽

1994 ◽

Vol 102 (3) ◽

pp. 195-198 ◽

Cited By ~ 1

Author(s):

J. L. Pannier ◽

P. Calders ◽

W. Eechaute

Keyword(s):

Adrenergic Receptor ◽

Conscious Dogs ◽

Plasma Testosterone ◽

Receptor Blockade ◽

Response To Exercise ◽

Adrenergic Receptor Blockade

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Calcium channel blockers induce preferential coronary vasodilation by an alpha 1-mechanism

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.1987.253.3.h604 ◽

1987 ◽

Vol 253 (3) ◽

pp. H604-H613

Author(s):

D. R. Knight ◽

S. F. Vatner

Keyword(s):

Calcium Channel ◽

Calcium Channel Blockers ◽

Total Peripheral Resistance ◽

Adrenergic Receptor ◽

Peripheral Resistance ◽

Channel Blockers ◽

Receptor Blockade ◽

Coronary Resistance ◽

Metabolic Demand ◽

Adrenergic Receptor Blockade

The effects of nitrendipine were evaluated on coronary and systemic dynamics in conscious dogs. Nitrendipine (8 micrograms X kg-1 X min-1) decreased late diastolic left circumflex coronary resistance (62 +/- 1.3%) significantly more (P less than 0.01) than total peripheral resistance (54 +/- 1.8%). After propranolol (1 mg/kg) and atropine methyl bromide (0.1 mg/kg) to eliminate reflex increases in myocardial metabolic demand, nitrendipine still reduced late diastolic coronary resistance (56 +/- 1.5%) significantly more (P less than 0.01) than total peripheral resistance (46 +/- 1.4%). However, after adding alpha 1-adrenergic receptor blockade with prazosin (1 mg/kg) to beta-adrenergic and cholinergic receptor blockades, nitrendipine no longer reduced late diastolic coronary resistance (40 +/- 2.7%) more than total peripheral resistance (45 +/- 2.1%) and, in fact, reduced late diastolic coronary resistance less than prior to prazosin. Nifedipine and diltiazem also reduced late diastolic coronary resistance more than total peripheral resistance prior to, but not after, alpha 1-adrenergic receptor blockade. In contrast, sodium nitroprusside reduced late diastolic coronary resistance more (P less than 0.01) than total peripheral resistance both before and after alpha 1-adrenergic receptor blockade. Thus calcium channel blockers preferentially dilate the coronary bed in comparison with the systemic circulation. Since the preferential effects were abolished by prazosin, an alpha 1-adrenergic mechanism is implicated.

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Effects of alpha-adrenergic receptor blockade on coronary circulation in conscious dogs

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.1982.243.1.h94 ◽

1982 ◽

Vol 243 (1) ◽

pp. H94-H98

Author(s):

P. Macho ◽

T. H. Hintze ◽

S. F. Vatner

Keyword(s):

Mean Arterial Pressure ◽

Arterial Pressure ◽

Adrenergic Receptor ◽

Coronary Circulation ◽

Conscious Dogs ◽

Receptor Blockade ◽

Receptor Blocking ◽

Blocking Agents ◽

Alpha Adrenergic Receptor ◽

Adrenergic Receptor Blockade

The effects of three alpha-adrenergic-receptor blocking agents (phentolamine, prazosin, and trimazosin) were compared on the coronary circulation and left ventricular (LV) function in chronically instrumented conscious dogs. The three alpha-adrenergic-receptor blocking agents were administered in equidepressor doses (mean arterial pressure fell by approximately 20%) and in the presence of beta-adrenergic-receptor blockade and constant heart rate. LV systolic pressure, LV end-diastolic pressure, and LV end-diastolic diameter also fell similarly with the three drugs. Phentolamine decreased the time rate of change of LV pressure (LV dP/dt) by 21 +/- 3%, whereas trimazosin and prazosin decreased LV dP/dt only by 14 +/- 2 and 11 +/- 2%, respectively. LV velocity was not changed with trimazosin and prazosin but decreased with phentolamine by 12 +/- 4%. The three drugs exerted differential effects on the coronary circulation. Only trimazosin increased coronary blood flow (18 +/- 5%). Trimazosin decreased late diastolic coronary resistance (LDCR) by 35 +/- 2%, which was significantly more than reductions in LDCR induced by prazosin (22 +/- 2%) and by phentolamine (11 +/- 3%). A test dose of phenylephrine (5.0 micrograms/kg) increased mean arterial pressure by 53 +/- 3.5 mmHg. After trimazosin, prazosin, and phentolamine, the same dose of phenylephrine increased mean arterial pressure by 24 +/- 2.1, 14 +/- 1.6, and 1.9 +/- 0.6 mmHg, respectively. The response after phentolamine was significantly less than with trimazosin (P less than 0.01) and prazosin (P less than 0.02). Thus the capacity of these three alpha-adrenergic-receptor blocking drugs to dilate coronary vessels is inversely proportional to their capability to block exogenous alpha-adrenergic-receptor agonists.

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Role of beta 2-adrenergic receptors on coronary resistance during exercise

Journal of Applied Physiology ◽

10.1152/jappl.1988.64.6.2287 ◽

1988 ◽

Vol 64 (6) ◽

pp. 2287-2293 ◽

Cited By ~ 25

Author(s):

S. E. DiCarlo ◽

R. W. Blair ◽

V. S. Bishop ◽

H. L. Stone

Keyword(s):

Adrenergic Receptors ◽

Adrenergic Receptor ◽

Receptor Blockade ◽

Coronary Resistance ◽

Alpha Adrenergic Receptor ◽

Daily Exercise ◽

Significant Difference ◽

Beta 2 ◽

Adrenergic Receptor Blockade

The effects of regional alpha- and specific beta 2-adrenergic receptor blockade on measurements of late diastolic coronary resistance (LDCR) and mean coronary blood flow velocity (CBFV) during exercise were examined in 14 conscious adult mongrel dogs. Specific beta 2-adrenergic receptor blockade (ICI 118.551) significantly decreased CBFV and increased LDCR by blockade of beta 2-vasodilator tone independent of alpha-adrenergic receptor-mediated tone and independent of altering myocardial metabolism. alpha-Adrenergic receptor blockade (phentolamine, 1 mg) significantly increased CBFV and decreased LDCR by blocking sympathetically mediated vasoconstrictor tone. There was no significant difference in the magnitude of response between alpha- and beta 2-adrenergic receptor blockade. These results demonstrate that alpha- and beta 2-adrenergic receptors have a significant and evidently equal influence on CBFV and LDCR during exercise. Four weeks of daily exercise and left stellate ganglionectomy (LSGx) prevented phentolamine-induced vasodilation but not ICI 118.551-induced vasoconstriction. This suggests that daily exercise and LSGx significantly decreased the alpha-adrenergic receptor-mediated vasoconstrictor tone on the coronary circulation, resulting in an apparently greater role for the coronary vascular beta 2-adrenergic receptor on the control of CBFV and LDCR during exercise.

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