Biomedical subjects

A C Bonham

Publications and source records attributed to A C Bonham.

44 records · Page 3Linked to original sources

PubMed1987

Electrical stimulation in perifornical lateral hypothalamus decreases coronary blood flow in cats.

Based on evidence implicating the central nervous system in the regulation of coronary vascular resistance and the knowledge that the hypothalamus is a central site for integration of cardiovascular control, studies were undertaken to determine if electrical stimulation in the hypothalamus produced coronary vasoconstriction. In anesthetized cats, following beta-adrenergic receptor blockade, stimulation in perifornical lateral hypothalamus produced a transient decrease in coronary blood flow velocity (30 +/- 5%), a small pressor effect (7 +/- 2 mmHg), and an initial decrease in hindquarter blood flow velocity (51 +/- 5%). The decrease in coronary flow velocity, which had an onset latency of 1-3 s and a duration of 5-15 s, was abolished by ipsilateral stellate ganglionectomy and by intravenous and intracoronary prazosin. The coronary vasoconstriction produced by hypothalamic stimulation was not different from that produced by cardioaccelerator nerve stimulation. These results suggest that electrical stimulation of a hypothalamic site produces an alpha-adrenergic receptor-mediated decrease in coronary blood flow that is unmasked by beta-adrenergic receptor blockade, requires the integrity of ipsilateral cardiac sympathetic innervation, and mimics the coronary response to cardioaccelerator nerve stimulation.

Adrenergic beta-Antagonists↗

PubMed1987

Neurogenic regulation of coronary blood flow: evidence for a central nervous system pathway.

The central representation of neurogenically mediated coronary vasoconstriction produced by activation of the sympathetic nervous system was examined in anesthetized cats instrumented for continuous recording of coronary and femoral blood flows, arterial pressure, and heart rate. Electrical stimulation in a small region of perifornical lateral hypothalamus increased arterial pressure, heart rate, and coronary blood flow; following the administration of propranolol, a transient coronary vasoconstrictor response was unmasked. The response was mediated over the sympathetic nervous system since it was blocked by stellate ganglionectomy and by the alpha 1-adrenergic receptor antagonist prazosin. Projections to and from the lateral hypothalamic site were identified by using anterograde and retrograde pathway-tracing techniques. Paraventricular nucleus projected to lateral hypothalamus, which in turn made connections in periaqueductal gray with projections terminating in lateral reticular formation of medulla. Coronary vasoconstrictor responses qualitatively identical to those produced by hypothalamic stimulation were found with activation of paraventricular nucleus and lateral reticular formation. Interruption of neuronal transmission in the medullary site blocked the response produced by activation of hypothalamic site. These data demonstrate that coronary vasoconstriction mediated over the sympathetic nervous system can be elicited from an interconnected pathway that links sympathoexcitatory sites in forebrain and brainstem.

Animals↗

PubMed1985

The cardiovascular effects of centrally and peripherally administered indoramin in conscious rats.

Indoramin has centrally mediated hypotensive effects in anesthetized animals. In the present study, the cardiovascular effect of central and peripheral indoramin was determined in conscious, freely moving rats. Animals were instrumented with femoral arterial and venous catheters and miniaturized pulsed-Doppler flow probes were placed on the superior mesenteric and renal arteries and lower abdominal aorta. Injection of indoramin (25-100 micrograms) in the lateral cerebroventricle produced an immediate (1.5 min) increase in arterial pressure which was accompanied by vasoconstriction in all three vascular beds. By 10 min all values had returned to control except for heart rate which was decreased. Vehicle alone or intravenous indoramin (100 micrograms) had no effect. In baroreceptor-denervated rats smaller effects were seen. Intravenous indoramin (3.0-13.5 mg/kg) produced dose-related decreases in arterial pressure, heart rate, and hindquarter vascular resistance. The 13.5 mg/kg dose blocked to a similar degree the cardiovascular effect produced by intravenous norepinephrine or stimulation of the paraventricular nucleus. These data suggest that indoramin is an effective peripheral alpha-adrenergic receptor antagonist but does not appear to be centrally active as a hypotensive agent.

Animals↗

PubMed1984

Comparative central and peripheral antihypertensive mechanisms of urapidil and prazosin.

The central effects of urapidil were investigated in conscious rats with sinoaortic denervation. Intraventricular urapidil administration (40 to 100 micrograms) produced a transient depressor response followed by a pressor response coupled with tachycardia. In comparison, intraventricular prazosin administration (2.5 to 5.0 micrograms) produced only a prolonged depressor effect. The effect of intravenously administered urapidil (3 mg/kg) on arterial pressure, heart rate, and mesenteric, renal, and hindquarter resistances was then compared with that of prazosin (0.5 mg/kg) in conscious rats with sinoaortic denervation, instrumented with pulsed Doppler flow probes. Both agents caused similar significant decreases in arterial pressure and vascular resistances, but urapidil decreased renal resistance significantly more than did prazosin. Prazosin increased heart rate, whereas no change was found with urapidil. Prazosin blocked the pressor and regional constrictor effects of intravenously administered norepinephrine more effectively than urapidil.

Animals↗

PubMed1984

Toxicity of oxygen radicals in cultured pulmonary endothelial cells.

Superoxide dismutase and catalase, which catalytically remove O-2 and H2O2, respectively, each separately protected cultured pulmonary artery endothelial cells from loss of membrane integrity after exposure to oxygen radicals generated either cellularly (polymorphonuclear leukocytes) or chemically (dihydroxyfumarate). Nicotinamide, a precursor of nicotinamide-adenine dinucleotide (NAD) and an inhibitor of ADP-ribose synthetase, also protected cultured endothelial cells from loss of membrane integrity in a concentration-dependent manner after exposure to DHF.

Animals↗

PubMed1984

A method for comparing the peak intensity and duration of action of aerosolized bronchodilators using bronchoprovocation with methacholine.

The effects of aerosolized metaproterenol (1.30 mg) and isoetharine (1.02 mg) on nonspecific airway responsiveness to inhaled methacholine were quantitated and compared in 6 asthmatic subjects for 4 h after dosing. Both metaproterenol and isoetharine demonstrated bronchodilatation and reduced airway responsiveness during the first hour. Isoetharine had lost its bronchodilator effects and its effects on airway responsiveness by 2.25 h. The effects of metaproterenol on airway responsiveness had decreased by half at 2.25 h, while its bronchodilator effect remained maximal. Metaproterenol had no effect on airway responsiveness by 4 h, despite persisting bronchodilatation. Thus, for metaproterenol, there is disparity between duration of bronchodilation and suppression of airway responsiveness. Because methacholine sensitivity is a measure of nonspecific airway responsiveness, which appears to correlate with the severity of asthma, this methodology may provide more relevant information for assessment of duration of effect and estimation of appropriate dosing intervals for maintenance therapy than do more traditional methods.

Adolescent↗

PubMed1984

Studies on the mechanism of the central antihypertensive effect of guanabenz and clonidine.

Mean arterial pressure and heart rate responses were measured following intracerebroventricular (i.c.v.) injections of guanabenz and clonidine in conscious intact, sinoaortic baroreceptor denervated (SAD) animals, and in SAD animals with anteroventral third ventricle (AV3V) or sham-AV3V lesions. These results suggest that in the conscious unrestrained rat: (1) the centrally-mediated depressor effect of guanabenz and clonidine is masked by intact baroreceptors; (2) the centrally mediated bradycardia is independent of baroreceptor function and (3) the integrity of the AV3V region is not required for expression of these central effects.

Animals↗

PubMedDate not supplied

Regional hemodynamic effects of antihypertensive renomedullary lipids in conscious rats.

Renomedullary tissue has been proposed to exert an antihypertensive endocrine-like action. The antihypertensive polar renomedullary lipids (APRL) and neutral renomedullary lipids (ANRL) are potential mediators of this action. We evaluated the blood pressure and regional hemodynamic responses to APRL administered peripherally (i.v.) and to the central nervous system (CNS) in normal rats and rats with sinoaortic deafferentation (SAD) to remove baroreflex buffering. Rats were chronically instrumented with Doppler flow probes for measurement of mesenteric, renal, and hind-quarter vascular resistance, with arterial pressure and intravenous catheters, and with lateral cerebroventricular cannuli for intracerebroventricular (i.c.v.) administration. Intravenous APRL (0.01 to 1.0 micrograms) produced a dose-dependent decrease in blood pressure, tachycardia, and dilation of all vascular beds studied. The dose-response relationships were shifted to the left in SAD animals. APRL administered i.c.v. had no effect on intact or SAD rats. Pressor and regional vasoconstrictor responses to norepinephrine, angiotensin, and vasopressin were markedly reduced in SAD animals during constant infusion of APRL. In a second group of conscious SAD animals instrumented for blood pressure and heart rate measurements, intravenous ANRL (500 micrograms) decreased both arterial pressure (-45 +/- 16 mm Hg) and heart rate (-50 +/- 16 bpm). When given i.c.v., however, ANRL (10-100 micrograms) had no significant effect on resting blood pressure or heart rate. These studies suggest that APRL and ANRL produce no significant cardiovascular effects that are mediated through the CNS. However, both lipids are potent depressor agents, and APRL exhibits a strong peripheral vasodilator action and nonspecifically reduces reactivity to vasoconstrictor agents.

Animals↗