Adrenergic denervation in rabbits with diabetes mellitus

1990 ◽  
Vol 259 (1) ◽  
pp. H55-H61 ◽  
Author(s):  
R. A. Cohen ◽  
B. Tesfamariam ◽  
R. M. Weisbrod ◽  
K. M. Zitnay
Keyword(s):  
Diabetes Mellitus ◽  
Smooth Muscle ◽  
Carotid Artery ◽  
Neuronal Uptake ◽  
Electrical Nerve Stimulation ◽  
Rabbit Carotid Artery ◽  
Diabetic Rabbit ◽  
Significant Difference ◽  
Increased Sensitivity ◽  
Neurogenic Vasoconstriction

The influence of alloxan-induced diabetes mellitus on the sympathetic neuroeffector junction of the rabbit carotid artery denuded of endothelium was studied. Six weeks of diabetes resulted in a neuropathy characterized by a 38% reduction in the arterial content of norepinephrine. Norepinephrine release from the nerves measured from electrically stimulated superfused arterial segments was decreased. The cocaine-sensitive accumulation of [3H]-norepinephrine (NE) was also reduced, reflecting decreased neuronal uptake. The consequences of these prejunctional changes were studied by measuring isometric contractions of arterial rings caused by electrical nerve stimulation or by exogenous norepinephrine. Despite the reduced release of norepinephrine, neurogenic contractions were normal, suggesting an increased sensitivity of the smooth muscle. After neuronal uptake was blocked, the neurogenic contractions of diabetic arteries were less than normal, reflecting the reduction in transmitter release. The sensitivity of diabetic arteries to exogenous norepinephrine was increased under control conditions; maximal contractions were unchanged. Blockade of norepinephrine uptake increased norepinephrine sensitivity more in normal than in diabetic arteries, and there was no longer a significant difference in sensitivity. Thus, under control conditions, neurogenic contractions of the partially denervated diabetic rabbit carotid artery are paradoxically normalized by increased alpha-adrenergic sensitivity of the smooth muscle. The increased sensitivity caused by reduced neuronal uptake can thus preserve neurogenic vasoconstriction and cause supersensitivity to exogenous catecholamines in the sympathetic neuropathy caused by diabetes mellitus.

Endothelium-dependent hyperpolarization elicited by adenine compounds in rabbit carotid artery

1991 ◽  
Vol 260 (4) ◽  
pp. H1037-H1042 ◽  
Author(s):  
G. Chen ◽  
H. Suzuki
Keyword(s):  
Smooth Muscle ◽  
Carotid Artery ◽  
Direct Action ◽  
Smooth Muscles ◽  
Muscle Membrane ◽  
Dependent Manner ◽  
Rabbit Carotid Artery ◽  
Mechanical Removal ◽  
Smooth Muscle Membrane ◽  
Adventitial Cells

Electrical responses of the membrane of intimal and adventitial smooth muscle cells of the rabbit carotid artery to ATP, ADP, AMP, and adenosine were recorded. In intimal cells, these compounds hyperpolarized the membrane. Mechanical removal of the endothelium altered the responses to ATP and ADP to one of a transient depolarization, with no alteration of the response to AMP and adenosine. In the adventitial cells, ATP and ADP produced a transient depolarization, whereas AMP and adenosine produced a sustained hyperpolarization, irrespective of the presence or absence of the endothelium. In tissues with an intact endothelium, 5'-adenylylimidodiphosphate tetralithium salt and alpha,beta-methylene ATP (mATP) transiently depolarized the membrane in these smooth muscles. In case of stabilization with mATP, only hyperpolarization was generated by ATP, in an endothelium-dependent manner. Our interpretation of these observations is that 1) ATP and ADP depolarize smooth muscle membrane by a direct action and hyperpolarize the membrane indirectly through the release of endothelium-derived hyperpolarizing factor, 2) AMP and adenosine hyperpolarize the membrane, independently of the endothelium, and 3) ATP receptors present on the endothelial cell membrane differ from those on smooth muscle membrane.

Endothelial and vascular smooth muscle responses are altered after left lung autotransplantation

1994 ◽  
Vol 266 (5) ◽  
pp. H2026-H2032 ◽  
Author(s):  
N. A. Flavahan ◽  
T. D. Aleskowitch ◽  
P. A. Murray
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Left Lung ◽  
Calcium Ionophore ◽  
Selective Reduction ◽  
Isometric Tension ◽  
Maximal Response ◽  
No Donor ◽  
Significant Difference ◽  
Increased Sensitivity

Left lung autotransplantation (LLA) increased the pulmonary vasoconstriction evoked by phenylephrine and attenuated the vasodilatation caused by acetylcholine or bradykinin in conscious dogs. To study the mechanisms responsible for these changes, pulmonary arterial rings were isolated from right (control) and left (LLA) lower lobes of dogs 1-26 mo after LLA and were suspended for isometric tension recording. Compared with control rings from the same anatomic location, contractions to phenylephrine were increased after LLA in rings with or without endothelium. In arterial rings contracted to 50% of their maximal response to phenylephrine, acetylcholine, bradykinin, and calcium ionophore caused endothelium-dependent relaxations that were reduced in LLA compared with control rings. In arterial rings from control and LLA lungs, relaxations to acetylcholine were not altered by inhibition of cyclooxygenase (indomethacin) but were reduced after inhibition of NO synthase [N omega-nitro-L-arginine methyl ester (L-NAME)]. After L-NAME, there was no longer any significant difference in acetylcholine-induced relaxation between arterial rings from control and LLA lungs. Relaxation to SIN-1, a NO donor, was similar in arterial rings (without endothelium) from control and LLA lungs. The results suggest that LLA causes an increased sensitivity of vascular smooth muscle to alpha 1-adrenergic activation and endothelial dysfunction that is mediated by a selective reduction in the activity of endothelium-derived relaxing factor/NO.

Digoxin-norepinephrine response and calcium blocker effects in vascular smooth muscle

1979 ◽  
Vol 236 (4) ◽  
pp. H613-H619
Author(s):  
S. F. Flaim ◽  
D. J. DiPette
Keyword(s):  
Smooth Muscle ◽  
Carotid Artery ◽  
Vascular Smooth Muscle ◽  
Calcium Antagonists ◽  
Constant Pressure ◽  
Lanthanum Chloride ◽  
Procaine Hydrochloride ◽  
Release Process ◽  
Rabbit Carotid Artery ◽  
Calcium Sequestration

The mechanism of potentiation by digoxin of the response of vascular smooth muscle to norepinephrine was investigated in 5-cm intact segments of rabbit carotid artery. Segments were mounted in a chamber and perfused at constant pressure while flow and upstream and downstream pressures were recorded and resistance was calculated. Each vessel was perfused with a submaximal vasoconstricting concentration of norepinephrine (6 x 10(-6)M) alone, in the presence of digoxin (6 x 10(-5)M), and during exposure to both digoxin and one of the following calcium antagonists: lanthanum chloride (5 x 10(-4)M procaine hydrochloride (5 x 10(-3)M), or verapamil (5 x 10(-5)M). Digoxin potentiated the response to norepinephrine alone by 20% (P less than 0.01), to norepinephrine plus lanthanum chloride by 10% (P less than 0.001), and to norepinephrine plus procaine hydrochloride by 17% (P less than 0.001). Digoxin did not potentiate the norepinephrine response in the presence of verapamil. These data suggest that the mechanism of digoxin potentiation of the norepinephrine response in vascular smooth muscle may involve an alteration in a cellular calcium sequestration or release process. The potential cellular sites that may contribute to this phenomenon are discussed.

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