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Relationship between plasma sodium concentration and vascular reactivity in man.

Experiments were done to study the effects of acute changes in plasma sodium concentration [Na] on vasoconstrictor responses to norepinephrine and to reflex sympathetic stimulation in man. [Na] in the venous return from the forearm of each of 21 normal subjects was reduced (to an average of 118 mEq/liter), increased (147 mEq/liter), and maintained within the normal range (140 mEq/liter) by means of infusions into the brachial artery of three solutions containing different [Na]. Mannitol or sucrose and disodium sulfate were substituted for sodium chloride to produce the desired changes in [Na] without changing blood osmolarity. Blood flow to the forearm (plethysmograph) increased during infusion of the three solutions, but the increase in flow was not related to [Na]. Vasoconstrictor responses to injections of norepinephrine and angiotensin into the brachial artery were reduced at low [Na] and augmented at high [Na]. Reflex vasoconstriction, activated by lower body negative pressure, was similarly affected by changes in [Na]. In the isolated, perfused gracilis muscle of dog vasoconstrictor responses to norepinephrine and to nerve stimulation were attenuated, and the extraction of norepinephrine by this muscle was smaller when plasma [Na] was reduced.

Adult↗

A novel pressor area at the medullo-cervical junction that is not dependent on the RVLM: efferent pathways and chemical mediators.

Chemical stimulation of a region extending from the most caudal ventrolateral medulla into the upper cervical spinal cord evoked large sympathetically mediated pressor responses. These responses were not dependent on the integrity of the rostral ventrolateral medulla (RVLM) and may be mediated by glutamatergic neurons embedded in the white matter that project to the thoracic spinal cord. We term this new region the medullo-cervical pressor area (MCPA). This region is distinct from the caudal pressor area, because blockade of the RVLM with muscimol inhibited this pressor response but not that evoked from the MCPA. This is the first study to provide functional evidence for a cardiovascular role for neurons in the cervical spinal cord white matter that innervate sympathetic preganglionic neurons (Jansen and Loewy, 1997). Using retrograde tracing, in combination with immunohistochemistry and in situ hybridization, we identified two groups of spinally projecting neurons in the region. Approximately 50% of neurons in one group were excitatory because they contained vesicular glutamate transporter 1 (VGluT1)/VGluT2 mRNA, whereas the other contained a mixed population of neurons, some of which contained either VGluT1/VGluT2 or GAD67 (glutamic acid decarboxylase 67) mRNA. Despite the fact that activation of the MCPA causes potent sympathoexcitation, it does not act to restore arterial pressure after chemical lesion of the RVLM so that a role for this novel descending sympathoexcitatory region remains to be elucidated.

Adrenergic alpha-Agonists↗

Functional study of the dermal microcirculation in systemic sclerosis.

To measure the effect of cooling on digital blood pressure we used a strain-gauge and photoplethysmograph, with an automatic cooling device. Eighteen patients were compared with 18 matched controls. Laser-doppler technique was used to measure the perfusion changes after heating a small area of the skin in 5 locations on the body, readings were given in perfusion units. Eighteen patients with systemic sclerosis were compared with 25 individuals with primary Raynaud's phenomenon and 30 healthy controls. Cooling to 10 degrees C caused a significant digital blood pressure drop of 58 mmHg in patients with systemic sclerosis and 61 mmHg in Raynaud's phenomenon, as compared with controls. The microcirculation in patients with systemic sclerosis responded in the same way to local heating as in the normal population, increasing the perfusion to the same extent. In conclusion, an unselected group of patients with systemic sclerosis have normal dermal microcirculatory response to heating in spite of severe cold intolerance.

Adaptation, Physiological↗

Adrenoceptors in the kidney: localization and pharmacology.

The kidney plays a key role in the regulation of blood pressure. The sympathetic nervous system can influence many aspects of kidney function in relation to blood pressure control, e.g. renal vascular tone, intrarenal renin release and tubular reabsorption of electrolytes and fluid. The intrarenal distribution of adrenoceptors has now been studied on the basis of modern receptor ligand binding techniques combined with microscopic studies. The preferential localization of each adrenoceptor subtype within the kidney is reviewed. Furthermore, an attempt is made to describe the functional correlation of the presence of different adrenoceptor subtypes. Finally, the possible role of renal adrenoceptor abnormalities in the pathogenesis of hypertension is discussed.

Animals↗

Control of the microcirculation of the inner ear.

In general, many similarities are seen between cerebral blood flow and cochlear blood flow in response to vasodilating drugs. Cochlear vessels appear to be weakly controlled by the adrenergic nervous system. Cholinergic agents dilate cochlear vessels, although the vasodilation in the cochlea does not necessarily cause an increase in cochlear blood flow because of the associated hypotension. The effect on the systemic circulation is too profound to make these agents clinically useful. Papaverine, dipyridamole, amyl nitrite, and the plasma kinins produce transient increases in cochlear blood flow. Ten per cent carbon dioxide and 90 per cent oxygen product progressive vasodilation as long as the mixture is inhaled. Hydralazine produces too profound an effect on systemic blood pressure. Histamine and betahistine increase cochlear blood flow but only in doses that produce bronchiospasm in the guinea pig. Nicotinic acid and nicotinyl tartrate have no effect on cochlear blood flow. If one considers safety and efficacy as well as patient tolerance, papaverine appears to be the drug of choice for increasing cochlear blood flow clinically. Histamine and betahistine appear to be acceptable alternatives. Betahistine is no longer available for clinical use because of the failure to demonstrate clinical efficacy of therapy.

Cochlea↗