It can be concluded that, contrary to the hypothesized improvement in treadmill time following L-citrulline ingestion, there is a reduction in treadmill time following L-citrulline ingestion over the 24 h prior to testing. The normal response of increased plasma insulin following high-intensity exercise is also not present in the L-citrulline condition, indicating that L-citrulline ingestion may reduce nitric oxide-mediated pancreatic insulin secretion or increased insulin clearance.

No abstract

No abstract

The mechanism causing renal vascular flow to vary less than proportional to changes in arterial-venous pressure gradient, was studied in isolated dog kidneys perfused with whole blood and with cell-free colloidal solutions. This autoregulation of renal flow rapidly deteriorated along with vascular reactivity to drugs when oxygenated polyvinyl-pyrrolidone-Locke solution was used for perfusion. This deterioration was prevented by the addition of plasma to the colloidal perfusate. During the first 2 seconds of suddenly raised arterial pressure, renal flow normally increased proportionately or slightly more than proportionately to the increase in arterial pressure; intrarenal venous pressure, needle tissue pressure and kidney weight rose simultaneously. During the next 4 seconds, increasing vascular resistance upstream from the intrarenal veins caused parallel reductions in renal flow, intrarenal venous pressure, needle tissue pressure and at times kidney weight. After brief rhythmical changes in prevenous segmental resistance, flow became steady to show intense autoregulation, while intrarenal venous pressure and needle tissue pressure remained relatively low. This genuine autoregulation of renal flow was abolished by cooling kidneys to 3 to 10 C, and by treatment with chloral hydrate and with procaine in concentrations rendering the smooth muscle of the renal blood vessels relatively inert to direct drug stimulants. On the other hand, at temperatures of 3 to 10 C., and usually with chloral hydrate treatment, a factitious and passive type of flow autoregulation was observed, caused by the effects of abnormally high tissue pressures. Renal flow autoregulation was not appreciably impaired by anesthetization of the intrarenal nerves by procaine in concentrations which did not simultaneously depress vascular smooth muscle reactivity. Yohimbine induced sympatholysis did not impair autoregulation, and Dibenzyline treatment to intrarenal sympatholysis depressed only slightly autoregulation of renal flow. It was not inhibited by γ-aminobutyric acid. Anoxic perfusion which did not appreciably depress the reactivity of intrarenal autonomic ganglia, impaired autoregulation moderately. The loss of autoregulation of renal flow, accompanied by vasoconstriction following severe hemorrhage in the kidney donor dog, was slowly reversible upon perfusion of the subsequently isolated kidney and was related to smooth muscle contracture within the arterial-arteriolar vasculature. It is concluded, that myogenic vasomotion in the renal arterial-arteriolar tree in response to the level of transmural vascular pressure is the fundamental cause of genuine renal circulatory autoregulation. It is furthermore suggested that the myocytes of the juxtaglomerular apparatus may act as myogenic pacemakers in the vasomotion responsible for the essentially perfect autoregulation of the normal kidney.

A technique of constant-flow perfusion of isolated segments of dog intestinal arteries was used to investigate the role of calcium in contractile excitation of vascular smooth muscle by epinephrine and potassium. Contractile responses of the arterial muscle to epinephrine, perfused at constant concentration, and to potassium, perfused at high concentration, were both promptly prevented by calcium deionizing accomplished by simultaneous perfusion with solutions containing ethylenediaminetetraacetate (EDTA) for the chelation of available calcium ions. Potassium-induced muscular contracture was removed in a few minutes and epinephrine-induced contractions of potassium-depolarized muscle were soon prevented by perfusion with solutions containing ionic species of EDTA which chelated calcium ions. In muscle depolarized by potassium and calcium deionized by perfusion with solution containing MgK 2 EDTA, the contractile responses to epinephrine were immediately restored by combined perfusate injection of calcium ion and epinephrine. Injections of isosmotic calcium chloride solution of subthreshold or threshold contractile strength, when the artery had been perfused with sodium chloride-rich solution and the muscle had been relaxed, produced much greater contractions during both potassium and epinephrine excitation. The contractions from injected calcium chloride solution were increased by epinephrine excitation of muscle already depolarized by the external application of potassium sulfate, as they were in the previously polarized or resting muscle excited by epinephrine. The thesis is advanced that the relative muscular contractions induced by standard injected volumes of isosmotic calcium chloride solution were a relative index of the calcium influx and calcium permeability of the arterial smooth muscle cells in the various experimental conditions prevailing. Equimolar injections of isosmotic calcium iodide solution produced greater muscular contractions than did injections of isosmotic calcium chloride solution. The possibility is discussed that transmembranous passage of calcium into vascular muscle cells occurs significantly in the form of associated ion pairs. A dual effect of potassium on vascular smooth muscle behavior was observed in that a previously contractile-inducing amount of injected potassium exerted a relaxing effect on the arterial segment perfused with low-potassium solution when the muscle was contracted by epinephrine. It is concluded that: (a) calcium is essentially involved in excitation-contraction coupling of vascular smooth muscle; (b) the calcium permeability and calcium influx of vascular smooth muscle is greatly increased during both epinephrine and potassium excitation of the muscle cells, and epinephrine accomplishes these calcium changes even in muscle already depolarized by potassium; (c) adrenergic neurohormones exert their vasoexcitatory contractile effect by a membrane reaction which is basically nonelectrical and which primarily triggers an increased permeability and influx of calcium into the vascular myoplasm; and (d) the migrated calcium activates intracellularly the myoplasmic events of vascular smooth muscle contraction.