Hypertension and cardiovascular hypertrophy during chronic catecholamine infusion in rats

Johnson, Mark D.; Grignolo, Alberto; Kuhn, Cynthia M.; Schanberg, Saul M.

doi:10.1016/0024-3205(83)90410-1

Cited by 60 publications

(22 citation statements)

References 29 publications

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“…Several groups (33)(34)(35) have shown that infusions of epinephrine that do not increase plasma concentration can lead to a sustained elevation ofblood pressure in rats. Brown (6,15) has proposed that the dissociation between the short plasma half-life of epinephrine and the slow decay of the tachycardia after its infusion is due to a cyclical process of re-uptake and release of epinephrine from cardiac nerves.…”

Section: (I) Experimental Designmentioning

confidence: 99%

Epinephrine facilitates neurogenic vasoconstriction in humans.

Floras¹,

Aylward²,

Victor³

et al. 1988

J. Clin. Invest.

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Numerous studies have suggested that epinephrine may facilitate neural release of NE. There have been no studies in humans that demonstrate the functional significance of this action. To determine whether epinephrine facilitates neurogenic vasoconstriction in humans, we contrasted forearm vasoconstrictor responses to a reflex stimulus (lower body negative pressure ILBNPI) and to intraarterial NE before, during, and 30 min after infusion of epinephrine (50 ng/min) or isoproterenol (10 or 25 ng/min) into a brachial artery. These doses had no systemic effects. We reasoned that if prejunctional stimulation of beta receptors by epinephrine and isoproterenol had functional significance, the vasoconstrictor response to LBNP would be potentiated in comparison to the response to NE (postjunctional mechanism).Studies were done on 23 normal male volunteers. Forearm blood flow was measured with a strain gauge plethysmograph and intraarterial pressure was recorded. The ratio of vasoconstrictor responses to LBNP/NE was used as an index of neural release of the neurotransmitter NE. This ratio increased during infusions of both epinephrine and isoproterenol. 30 min after epinephrine the vasoconstrictor response to LBNP (n = 15) was augmented from +9.9±2.2 (SE) resistance units (RU) before epinephrine to +16.4±3.2 RU (P < 0.05); whereas the response to NE (n = 8) tended to decrease from +8.8±3.1 RU before to +4.2±1.2 RU after epinephrine (P > 0.05). In contrast, 30 min after isoproterenol the vasoconstrictor responses to LBNP and NE were the same as before isoproterenol. The augmented ratio of responses to LBNP/NE after epinephrine and not after isoproterenol supports the concept that epinephrine, but not isoproterenol, is taken up by the adrenergic terminal, is released subsequently during reflex stimulation, and augments the release of the neurotransmitter NE.These experiments provide the first hemodynamic evidence in humans that epinephrine and isoproterenol facilitate neurogenic vasoconstriction. The sustained effect of epinephrine in contrast to isoproterenol suggests that the late facilitation Parts of this work were presented at

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Section: (I) Experimental Designmentioning

confidence: 99%

Epinephrine facilitates neurogenic vasoconstriction in humans.

Floras¹,

Aylward²,

Victor³

et al. 1988

J. Clin. Invest.

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“…Besides the vasoactive actions of norepinephrine (NE), there is growing evidence that NE may be a trophic mediator for vascular smooth muscle cells (SMCs) and adventitial fibroblasts (AFBs). In vivo studies using surgical or systemic sympathetic denervation (16), systemic infusion of catecholamines (7,21), or ␣-adrenoceptor (AR) antagonists (20), as well as positive correlation of plasma catecholamines with wall hypertrophy and stiffness (8) and severity of atherosclerosis (22) in humans, suggest that NE may have direct trophic effects on the normal and diseased vascular wall. Moreover, in the ballooninjured rat and rabbit carotid, chronic systemic ␣ 1 -AR antagonists reduced cell proliferation, neointimal growth, and restenosis by at least 50% (14,18,30,34).…”

mentioning

confidence: 99%

“…It is possible that the different responses reflect differences in the in vitro and in vivo models or to duration of exposure and concentration of NE. Vascular wall hypertrophy is commonly observed with chronic systemic infusion of NE, although past studies have only examined doses that raise arterial pressure (7,20,21,24,32). However, physiological sympathoexcitation simultaneously increases both wall NE and arterial pressure.…”

mentioning

confidence: 99%

α₁-Adrenoceptor stimulation directly induces growth of vascular wall in vivo

Erami

Zhang

et al. 2002

American Journal of Physiology-Heart and Circulatory Physiology

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Previous studies suggesting that norepinephrine is directly trophic for the vascular wall have been confounded by concomitant hemodynamic disturbances. Herein, a microcatheter connected to an osmotic minipump was implanted adjacent to the rat carotid for 2-wk perivascular suffusion of agents at systemic levels ϳ1,000 times below the threshold for altering arterial pressure. Norepinephrine decreased lumen and adventitial areas and circumference by 10, 14, and 5%, respectively (all P Ͻ 0.05); a nonsubtype-specific ␣ 1-adrenoceptor (AR) antagonist had no effect. When begun at the time of balloon injury, 2-wk norepinephrine increased lumen loss by 45%, increased neointimal area by 64% and collagen content by 33%, and reduced vessel circumference by 5% (all P Ͻ 0.05). ␣ 1-AR antagonists decreased neointimal area by 33% (all P Ͻ 0.05). ␣ 1A-AR antagonist reduced lumen loss by 70%, neointimal area by 54%, circumference decline by 84%, and adventitial thickening by 87% (all P Ͻ 0.05), whereas ␣ 1B-, ␣1D-, ␣2-and ␤-AR antagonists were without effect. These are the first in vivo studies demonstrating that norepinephrine is directly trophic for the vascular wall and augments injury-induced intimal lesion growth. artery; smooth muscle; adventitia; injury; adrenergic VASCULAR HYPERTROPHY and remodeling are adaptive structural changes in response to sustained increases in arterial pressure or altered shear stress that favor restoration of normal physiological regulation. On the other hand, excessive wall growth, fibrosis, and inward or inadequate outward remodeling cause failure of surgical procedures (e.g., restenosis after angioplasty/ stent, atherectomy, and bypass grafting) and underlie diseases such as atherosclerosis, pulmonary hypertension, and accelerated arteriosclerosis (31,35). Thus the mechanisms regulating growth of vascular wall cells are under intense investigation. Besides the vasoactive actions of norepinephrine (NE), there is growing evidence that NE may be a trophic mediator for vascular smooth muscle cells (SMCs) and adventitial fibroblasts (AFBs). In vivo studies using surgical or systemic sympathetic denervation (16), systemic infusion of catecholamines (7, 21), or ␣-adrenoceptor (AR) antagonists (20), as well as positive correlation of plasma catecholamines with wall hypertrophy and stiffness (8) and severity of atherosclerosis (22) in humans, suggest that NE may have direct trophic effects on the normal and diseased vascular wall. Moreover, in the ballooninjured rat and rabbit carotid, chronic systemic ␣ 1 -AR antagonists reduced cell proliferation, neointimal growth, and restenosis by at least 50% (14,18,30,34). ␣ 1 -AR antagonists also attenuated angiotensin II-induced DNA synthesis (33) and atherogenesis (26,29). However, interpretation of these past in vivo studies is complicated by concomitant hemodynamic disturbances that, themselves, have trophic effects. For example, chemical or immunological systemic denervation and systemic ␣-AR antagonists cause significant hypotension and humoral changes. A...

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“…For example, hyperactivity of the sympathetic nervous system induced by sinoaortic denervation (6,7) even in the acute phase is capable of eliciting LVH in male rats (8). Furthermore, chronic administration of the sympathomimetic drug isoproterenol produces cardiac hypertrophy in rats (9)(10)(11)(12). However, little is known about the influence of renal sympathetic nerve activity on LVH.…”

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confidence: 99%

Diverse effects of renal denervation on ventricular hypertrophy and blood pressure in DOCA-salt hypertensive rats

Cabral

Silva

Gardioli

et al. 1998

Braz J Med Biol Res

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Cardiac hypertrophy that accompanies hypertension seems to be a phenomenon of multifactorial origin whose development does not seem to depend on an increased pressure load alone, but also on local growth factors and cardioadrenergic activity. The aim of the present study was to determine if sympathetic renal denervation and its effects on arterial pressure level can prevent cardiac hypertrophy and if it can also delay the onset and attenuate the severity of deoxycorticosterone acetate (DOCA)-salt hypertension. DOCA-salt treatment was initiated in rats seven days after uninephrectomy and contralateral renal denervation or sham renal denervation. DOCA (15 mg/kg, sc) or vehicle (soybean oil, 0.25 ml per animal) was administered twice a week for two weeks. Rats treated with DOCA or vehicle (control) were provided drinking water containing 1% NaCl and 0.03% KCl. At the end of the treatment period, mean arterial pressure (MAP) and heart rate measurements were made in conscious animals. Under ether anesthesia, the heart was removed and the right and left ventricles (including the septum) were separated and weighed. DOCA-salt treatment produced a significant increase in left ventricular weight/body weight (LVW/BW) ratio (2.44 ± 0.09 mg/g) and right ventricular weight/body weight (RVW/BW) ratio (0.53 ± 0.01 mg/g) compared to control (1.92 ± 0.04 and 0.48 ± 0.01 mg/g, respectively) rats. MAP was significantly higher (39%) in DOCA-salt rats. Renal denervation prevented (P>0.05) the development of hypertension in DOCA-salt rats but did not prevent the increase in LVW/BW (2.27 ± 0.03 mg/g) and RVW/BW (0.52 ± 0.01 mg/g). We have shown that the increase in arterial pressure level is not responsible for cardiac hypertrophy, which may be more related to other events associated with DOCA-salt hypertension, such as an increase in cardiac sympathetic activity. Correspondence

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Hypertension and cardiovascular hypertrophy during chronic catecholamine infusion in rats

Cited by 60 publications

References 29 publications

Epinephrine facilitates neurogenic vasoconstriction in humans.

Epinephrine facilitates neurogenic vasoconstriction in humans.

α₁-Adrenoceptor stimulation directly induces growth of vascular wall in vivo

Diverse effects of renal denervation on ventricular hypertrophy and blood pressure in DOCA-salt hypertensive rats

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Hypertension and cardiovascular hypertrophy during chronic catecholamine infusion in rats

Cited by 60 publications

References 29 publications

Epinephrine facilitates neurogenic vasoconstriction in humans.

Epinephrine facilitates neurogenic vasoconstriction in humans.

α1-Adrenoceptor stimulation directly induces growth of vascular wall in vivo

Diverse effects of renal denervation on ventricular hypertrophy and blood pressure in DOCA-salt hypertensive rats

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α₁-Adrenoceptor stimulation directly induces growth of vascular wall in vivo