Central Vasomotor Stimulation by Angiotensin
TL;DR: Angiotensin was infused at low rates into the vertebral arteries of anaesthetized dogs, and when infused at similar rates intravenously or into the internal carotid artery it either did not change blood pressure, or raised it only very slightly, suggesting that part of the pressor effect of intravenous ang Elliotensin may be mediated by a direct stimulation of some parts of the hind brain.
Abstract: SUMMARY 1. When angiotensin was infused at low rates into the vertebral arteries of anaesthetized dogs, it raised the blood pressure. When infused at similar rates intravenously or into the internal carotid artery it either did not change blood pressure, or raised it only very slightly. The difference in response was highly significant over the range of 1-50 ng kg- ' min- '. 2. During intravenous infusion at higher rates, angiotensin usually produced the well-known reflex bradycardia and fall of cardiac output, but on infusion into the vertebral arteries it rapidly raised systemic arterial pressure, often increased heart rate, and usually produced a transient increase of cardiac output. 3. Angiotensin by both routes raised peripheral resistance, but noradrenaline, by contrast, produced the same response whether it was given into the vertebral arteries or into a vein. 4. These observations suggest that part of the pressor effect of intravenous angiotensin may be mediated by a direct stimulation of some part of the hind brain. There are several means by which angiotensin may raise systemic arterial pressure. In addition to its direct arterial vasoconstrictor action, it can release catecholamines from the adrenal medulla (Braun-Menhdez, Fasciolo, Leloir & Muiioz, 1940), stimulate or facilitate transmission in sympathetic ganglia (Lewis & Reit, 1966) and enhance the peripheral vasoconstrictor response to endogenously released noradrenaline (McCubbin & Page, 1963a, b). In very large doses it was reported, 9 years ago, to cause central stimulation of the sympatho-adrenal system when infused into the the dog's cerebral circulation which was isolated and perfused from another animal (Bickerton & Buckley, 1961). The special importance of the vertebral artery territory in mediating the central stimulatory effects of angiotensin, and the extreme sensitivity to angiotensin when given into the vertebral artery, was first observed in conscious rabbits (Dickinson, 1965; Yu & Dickinson, 1965) and in anaesthetized rabbits after blood
Citations
More filters
TL;DR: A large body of data is now available to support the existence of numerous organ-based RAS exerting diverse physiological effects, and universal paracrine and autocrine actions may be important in many organ systems and can mediate important physiological stimuli.
Abstract: Since the first identification of renin by Tigerstedt and Bergmann in 1898, the renin-angiotensin system (RAS) has been extensively studied. The current view of the system is characterized by an increased complexity, as evidenced by the discovery of new functional components and pathways of the RAS. In recent years, the pathophysiological implications of the system have been the main focus of attention, and inhibitors of the RAS such as angiotensin-converting enzyme (ACE) inhibitors and angiotensin (ANG) II receptor blockers have become important clinical tools in the treatment of cardiovascular and renal diseases such as hypertension, heart failure, and diabetic nephropathy. Nevertheless, the tissue RAS also plays an important role in mediating diverse physiological functions. These focus not only on the classical actions of ANG on the cardiovascular system, namely, the maintenance of cardiovascular homeostasis, but also on other functions. Recently, the research efforts studying these noncardiovascular effects of the RAS have intensified, and a large body of data are now available to support the existence of numerous organ-based RAS exerting diverse physiological effects. ANG II has direct effects at the cellular level and can influence, for example, cell growth and differentiation, but also may play a role as a mediator of apoptosis. These universal paracrine and autocrine actions may be important in many organ systems and can mediate important physiological stimuli. Transgenic overexpression and knock-out strategies of RAS genes in animals have also shown a central functional role of the RAS in prenatal development. Taken together, these findings may become increasingly important in the study of organ physiology but also for a fresh look at the implications of these findings for organ pathophysiology.
1,543 citations
1,312 citations
TL;DR: The renin-angiotensin system appears to have an important role in the elevated SVR in some patients with heart failure, and chronic inhibition of converting enzyme should be explored as a possible therapeutic approach.
Abstract: In 15 patients with severe chronic left ventricular failure, plasma renin activity (PRA) ranged widely, from 0.2--39 ng/ml/hr. The level of PRA was unrelated to cardiac output (CO) or pulmonary artery wedge pressure (PWP), but was slightly negatively correlated with mean arterial pressure (MAP) (r = -0.45) and systemic vascular resistance (SVR) (r = -0.40). After infusion of the angiotensin converting enzyme inhibitor teprotide (SQ 20,881) PWP fell from 26.3 +/- 1.3 (SEM) to 20.3 +/- 1.4 mm Hg (P less than 0.001), CO rose from 3.94 +/- 0.23 to 4.75 +/- 0.31 l/min (P less than 0.001), MAP fell from 87.5 +/- 3.8 to 77.9 +/- 4.1 mm Hg (P less than 0.001) and SVR from 1619 +/- 148 to 1252 +/- 137 dyne-sec-cm-5 (P less than 0.001). The fall in MAP and in SVR was significantly correlated with control PRA (r = 0.68 and r = 0.58, respectively). When subjects were divided on the basis of control PRA the hemodynamic response to teprotide was greatest in the high renin group. PRA rose after teprotide (8.7 +/- 3.4 to 37.9 +/- 7.7 ng/ml/hr, P less than 0.05) but plasma norepinephrine fell (619.1 +/- 103.6 to 449.7 +/- 75.7, P less than 0.05). The renin-angiotensin system thus appears to have an important role in the elevated SVR in some patients with heart failure. Chronic inhibition of converting enzyme should be explored as a possible therapeutic approach.
391 citations
TL;DR: During recent years the nature of the considerable contribution of the sympathetic nervous system to renal hypertension has become somewhat more clear, due in part to the unexpected discoveries that angiotensin is not simply a direct vasoconstrictor agent but is almost ubiquitous in its actions.
Abstract: • During recent years the nature of the considerable contribution of the sympathetic nervous system to renal hypertension has become somewhat more clear, due in part to the unexpected discoveries that angiotensin is not simply a direct vasoconstrictor agent but is almost ubiquitous in its actions. Among these actions are several on the sympathetic nervous system that appear to intensify its effects on the peripheral vascular system. It stimulates release of catechols from the adrenal medulla (1); at certain dose levels it facilitates ganglionic transmission (2); and it sensitizes the neurovascular effector so that the effects of sympathetic vasomotor discharge are augmented (3). This latter effect may depend in part on prevention of reuptake of released norepinephrine (4). For a long time it was considered unlikely that angiotensin had any effect on the central nervous system since theoretically it does not cross the blood-brain barrier. Then Bickerton and Buckley (5), in 1961, cross-perfused the head of a recipient dog, isolated from its own circulation and connected to the body only by the spinal cord, with blood from a donor animal. When angiotensin was injected into the circulation of the donor animal it raised the systemic arterial pressure in the recipient's trunk as well as in the donor animal. Because
373 citations
TL;DR: An increase in the patients' blood pressure and age is associated with a progressive reduction in /3-adrenoreceptor sensitivity and/or reactivity, which may result in unopposed a- adreooreceptor-mediated vasoconstriction and thereby contribute to the development of hypertension.
Abstract: The role of the sympathetic nervous system as it relates to adrenoreceptor-mediated hemodynamic responses was investigated in patients with essential hypertension and in normal subjects of similar age. An age-related increase in plasma norepinephrine (PNE) concentrations observed in 36 recumbent normal subjects (r = 0.623, p less than 0.001) was not found in 56 patients; the latter included some young patients with high values. Sympathetic overactivity in patients (n = 24) as compared with normotensive subjects (n = 20) was suggested by a greater increase in PNE upon standing (242 +/- 34 vs 155 +/- 25 pg/ml (SEM), p less than 0.05) and persistently higher plasma epinephrine (PE) concentrations at rest and during equieffective exercise (p less than 0.05). In patients, PNE was directly related to systolic (r = 0.57, p less than 0.01) and diastolic (r = 0.53, p less than 0.01) blood pressure. Older age was associated with diminished exercise tachycardia and increased blood pressure responses to exercise, which were both more pronounced in hypertensive patients. This higher pressure/lower heart rate pattern was paralleled by an age-related decrease in isoproterenol sensitivity in normal subjects (0.97 +/- 0.15 in six below age 34 years, 1.31 +/- 0.30 in eight between 35--49 years, and 1.82 +/- 0.12 microgra/m2 in six above 50 years), which was also more pronounced (p less than 0.05) in hypertensive patients (1.20 +/- 1.18 in seven below age 34 years, 2.42 +/- 0.30 in nine between 35--49 years, and 6.73 +/- 2.44 micrograms/m2 in eight above 50 years). Thus, an increase in the patients' blood pressure and age is associated with a progressive reduction in beta-adrenoreceptor sensitivity and/or reactivity. Defective beta-adrenoreceptor-mediated responses may result in unopposed alpha-adrenoreceptor-mediated vasoconstriction and thereby contribute to the development of hypertension.
321 citations
References
More filters
TL;DR: Angiotensin II appears to produce an increase in blood pressure by a central hypertensive effect, probably due to stimulation of central sympathetic structures and evoking peripheral sympathetic discharges, which is blocked by administration of a sympatholytic agent into the peripheral circulation.
Abstract: SummaryAngiotensin II appears to produce an increase in blood pressure by 2 mechanisms: 1. A direct peripheral action on the vascular smooth musculature producing a marked increase in peripheral resistance, which is not blocked by piperoxan. 2. A central hypertensive effect, probably due to stimulation of central sympathetic structures and evoking peripheral sympathetic discharges, which are blocked by administration of a sympatholytic agent into the peripheral circulation.
378 citations
TL;DR: By intensifying the effect of normal neurogenic vasomotor activity, this action of angiotensin, along with the upward shift of threshold and range of response of the carotid sinus buffer mechanism, might account to a major degree for the large neurogenic component of chronic renal hypertension.
Abstract: Angiotensin has an effect on the sympathetic nervous system which results in an enhanced response to agents and procedures that cause release of endogenous norepinephrine while having little or no effect on response to exogenous norepinephrine. The effect is peripheral, it does not appear to involve sensitization of norepinephrine receptors, it is dependent upon a functionally intact sympathetic nervous system, and it appears unrelated to the direct vasoconstrictor action of angiotensin. The response to tyramine is increased in both acute and chronic renal hypertension; this suggests that only very small amounts of angiotensin, difficult to detect by present assay methods, continue to have an effect on the sympathetic nervous system in chronic renal hypertension. By intensifying the effect of normal neurogenic vasomotor activity, this action of angiotensin, along with the upward shift of threshold and range of response of the carotid sinus buffer mechanism, might account to a major degree for the large neurogenic component of chronic renal hypertension.
132 citations
TL;DR: The threshold for any detectable rise of systemic arterial pressure during the prolonged intravenous administration of angiotensin to conscious rabbits was observed to be an infusion rate of 0·003‐0·006 μg.
Abstract: 1. The threshold for any detectable rise of systemic arterial pressure during the prolonged intravenous administration of angiotensin to conscious rabbits was observed to be an infusion rate of 0·003-0·006 μg.kg−1.min−1.
2. At infusion rates between threshold and 0·04 μg.kg−1.min−1 the systemic arterial pressure rose progressively over a 3- to 7-day period to a plateau.
3. On stopping the angiotensin infusion the blood pressure fell rapidly back to its base line much faster than it rose during the infusion. The time taken to reach control values was approximately related to the duration of the infusion.
4. At infusion rates of about 0·05 μg.kg−1.min−1 the full rise of blood pressure developed within a few minutes, and could be sustained without change for many days. At higher rates the blood pressure diminished with time.
5. Diurnal fluctuations of blood pressure were often seen during prolonged infusions of angiotensin at low rates; and more rapid fluctuations of blood pressure over an hour or two were frequently encountered immediately after an infusion was turned off.
6. The possible role of angiotensin in producing chronic renal hypertension is discussed in the light of these observations.
26 citations