This is accomplished by engineering more neural control (not just depending on muscle metabolites to dilate the blood vessels in deep organs). Because blood flow in the capillaries is not uniform and depends chiefly on the contractile state of the arterioles, which when combined with increased cardiac ouput it puts more pressure on the capillaries. Due to the ability of smooth muscle sphincters of the pre-capillary vessels, the arterioles, to constrict when stretched, increased blood flow causes more pressure to be put on the capillary networks. By changing the action adrenaline and the sympathetic nervous system from vasoconstriction to vasodilation with the release of adenosine in the abdomen (circulating from there to the rest of the body including skeletal muscle) Body'Fit pHx achieves greater blood flow throughout the body. With blood pressure increased due to increased cardiac output, and with more uniform constriction in the arterioles... the best overall effect is achieved as the maximum number of arterioles are recruited providing for optimal total body vascular conditioning. When the neurotransmitters norepinephrine and epinephrine are released, they bind to alpha-adrenergic receptors on vascular smooth muscle, stimulating the constriction of the afferent arterioles. In turn, this indirectly stimulates the renin-angiotensin mechanism by stimulating the macula densa cells.

There are three principal mechanisms that function together to control renal blood flow. These are: renal autoregulation (the intrinsic system), neural control, and the rennin-angiotensin (hormonal) system.

Intrinsic Controls: Renal Autoregulation

Under normal conditions, glomerular blood pressure is regulated by the kidney’s autoregulatory system. Renal autoregulation involves controlling the diameter of the afferent and efferent arterioles. This is achieved by two types of control: myogenic reflex that responds to pressure changes in the renal blood vessels; and a tubuloglomerular feedback that detects changes in the juxtaglomerular apparatus.

The Myogenic Reflex: occurs due to the tendency of smooth muscle to contract when it is stretched. Increased systemic blood pressure causes the afferent arterioles to constrict. This reduces blood flow to the glomerulus, and prevents glomerular blood pressure reaching potentially damaging high levels. Conversely, a decrease in systemic blood pressure causes the afferent arterioles to dilate and glomerular hydrostatic pressure increases.

Tubuloglomerular Feedback: is controlled by the macula densa cells of the juxtaglomerular apparatus. These cells are sensitive to filtrate flow rate and osmotic signals. When they detect slow flowing filtrate, or filtrate with low osmolarity, they induce vasodilation of the afferent arterioles. However, when filtrate flow is rapid, and/or the filtrate has a high sodium and chloride concentration, the macula densa cells induce the juxtaglomerular cells to secrete a chemical, which in turn induces vasoconstriction of the afferent arterioles. This reduces blood flow into the glomerulus, which in turn decreases the GFR and allows more time for filtrate processing.

Together, these mechanisms of renal autoregulation are able to maintain a relatively constant blood flow through the kidneys, while arterial pressure can fluctuate between 80 to 180 mmHg. This prevents large fluctuations in water and solute excretion.

Sympathetic Nervous System Controls

During periods of extreme stress, when blood flow has to be redirected to the heart, brain and skeletal muscles, renal autoregulatory mechanisms may be overridden. When this occurs, the neurotransmitters norepinephrine and epinephrine are released, and they bind to alpha-adrenergic receptors on vascular smooth muscle, stimulating the constriction of the afferent arterioles and inhibiting filtrate production. In turn, this indirectly stimulates the renin-angiotensin mechanism by stimulating the macula densa cells.

Norepinephrine also binds to beta-adrenergic receptors on the juxtaglomerular cells, inducing them to secrete renin, which in turn causes an increase in systemic blood pressure via the renin-angiotensin mechanism.

Renin-Angiotensin Mechanism

The principal function of this hormonal system is to maintain homeostasis of systemic blood pressure. However, it also acts indirectly to maintain the GFR of kidneys. Smooth muscle cells in the arteriole contract in response to the hormone angiotensin II (derived from angiotensinogen by an enzymatic cascade). This restricts blood flow causing average arterial blood pressure to rise.

This system’s influence on the GFR stems from the fact that there are more angiotensin receptors in the efferent arterioles than the afferent arterioles. This means that in the presence of angiotensin, the efferent arterioles constrict to a greater degree, thereby increasing the glomerular blood pressure, and restores a normal GFR.

In addition to the control systems described above, the kidneys are influences by a wide variety of other signalling systems. Many of these are dependent on chemical molecules, secreted by the kidneys themselves. These biologically active lipids are known as paracrine hormones.

Prostaglandins: PGE2, PGI2 are both vasodilators produced by the kidneys in response to sympathetic nervous stimulation and angiotensin II. They are believed to balance the increase in blood pressure induced by norepinephrine and angiotensin II.

Nitric Oxide (NO): Is a vasodilator which is produced by the vascular endothelium.

Adenosine: In the systemic system this molecule behaves as a vasodilator. However, it causes the renal vasculature to constrict. The identity of the vasoconstrictor in the previously described tubuloglomerular mechanism may be adenosine.

Endothelin: Is a vasoconstrictor that is secreted by the vascular endothelium and selected tubule cells.

Bradykinin: Is a vasodilator that indirectly increases GFR by stimulating the release of NO and prostaglandins.

Atrial Natriuretic Peptide: Is secreted by the heart, especially under conditions of high systemic blood pressure. ANP causes vasodilation of the afferent arteriole and vasoconstriction of the efferent arteriole, with an overall effect of slightly increasing GFR.

Adenosine Triphosphate: Many cell types release ATP into the renal interstitial fluid. Under different conditions ATP will have different effects on GFR. Sometimes ATP will cause the afferent arteriole to contract and GFR decreases, at other times, ATP may stimulate NO release and GFR increases.

Glucocorticoid: Drugs administered therapeutically to increase GFR. Glucocorticoids are also produced by the adrenal cortex as part of the stress response.

Histamine: Local release of histamine increases renal blood flow without increasing GFR by decreasing the resistance of the afferent and efferent arterioles.

Dopamine: Is a vasodilator that is secreted by the proximal tubule. This hormone has multiple functions in the kidney, including increasing the renal blood flow and inhibiting renin secretion.

Mechanisms of Transmembrane Transport

Passive Transport

The movement of ions and solutes across a membrane is passive if the movement is spontaneous and it does not require direct expenditure of metabolic energy.

Simple Diffusion

This occurs if a substance is transported along its electrochemical gradient (i.e., from a region of high concentration to a region of low concentration, or to a region of opposite charge). Lipid-soluble substances such as the gases O2, CO2 and NH3 diffuse directly across the lipid bilayer of the plasma membrane down their electrochemical gradients.

Facilitated Diffusion

In facilitated diffusion, particle transport is dependent on an interaction with a specific transmembrane protein that facilitates its movement across the plasma membrane.

Examples include:

Channels: Ions such as Na+ and K+ diffuse through hydrophilic, transmembrane protein channels. As charged particles they are unable to diffuse directly through the hydrophobic, lipid bilayer of the plasma membrane.

Uniporters: Transmembrane transporter proteins bind a specific particle on one side of the membrane; this induces a conformational change in the protein, which then results in the release of the particle on the other side of the membrane. Urea and glucose are transported across the membrane in this way.

Coupled Transporters: Are transmembrane transporter proteins that couple the transport of two or more solutes, in the same direction – symporters – and in opposite directions – antiporters - across the plasma membrane. One solute is usually transported down its electrochemical gradient, and the free energy released by this movement is harnessed to drive the energetically unfavourable transport of the other solute against its electrochemical gradient. This is also known as secondary active transport, to emphasise the fact that the energy used to drive the transport of the substance against its electrochemical gradient is not derived from the hydrolysis of ATP.

Solvent Drag

Water diffusion occurs through channels in the plasma membrane and it is driven by osmotic gradients. Dissolved solutes in the water are also carried along with it, in a process known as solvent drag. This accounts for a significant amount of solute reabsorption across the proximal tubule.

Active Transport

Transport is defined as being active if it is directly coupled to energy derived from metabolic processes. Substances are moved against their electrochemical gradients diven by the free energy released from the hydrolysis of ATP.

Endocytosis

Is the process of moving a substance across the plasma membrane in a vesicle. The plasma membrane invaginates and folds around the particle, until it pinches off and forms a vesicle within the cytoplasm. Because endocytosis requires ATP it can be regarded as a method of active transport.

Norepinephrine also binds to beta-adrenergic receptors on the juxtaglomerular cells, inducing them to secrete renin, which in turn causes an increase in systemic blood pressure via the renin-angiotensin mechanism.