Arteriolar wall

Acutely, diuretics lower BP by causing diuresis. The reduction in plasma volume and stroke volume associated with diuresis decreases cardiac output and, consequently, BP. The initial drop in cardiac output causes a compensatory increase in peripheral vascular resistance. With chronic diuretic therapy, the extracellular fluid volume and plasma volume return almost to pretreatment levels, and peripheral vascular resistance falls below its pretreatment baseline. The reduction in peripheral vascular resistance is responsible for the long-term hypotensive effects. Thiazides lower BP by mobilizing sodium and water from arteriolar walls, which may contribute to decreased peripheral vascular resistance. 

Little TL, Xia J, Duling BR Dye tracers define differential endothelial and smooth muscle coupling patterns within the arteriolar wall. Circ Res 1995 76 49-504. 

The reaction of the arteriolar wall to changes in the blood pressure is considered to consist of a passive, elastic component in parallel with an active, muscular response. The elastic component is determined by the properties of the connective tissue, which consists mostly of collagen and elastin. The relation between strain e and elastic stress ae for homogeneous soft tissue may be described as [18] ... 

At least for a first approach, the active component in the strain-stress relation may be treated in a simple manner. For some strain emax the active stress aa is maximum, and on both sides the stress decreases almost linearly with e — emax. Moreover, the stress is proportional to the muscle tone xjr. By numerically integrating the passive and active contributions across the arteriolar wall, one can establish a relation among the equilibrium pressure Peq, the normalized radius r, and the activation level xjr [19]. This relation is based solely on the physical characteristics of the vessel wall. However, computation of the relation for every time step of the simulation model is time-consuming. To speed up the process we have used the following analytic approximation [12] ... 

Figure 12.4 shows the relation between the equilibrium transmural pressure Peq and the normalized arteriolar radius r for different values of the muscular activation xj/. Fully drawn curves represent the results of a numerical integration of the active and passive stress components across the arteriolar wall, and the dashed curves represent the analytic approximation Eq. (17). 

As demonstrated by the power spectra in Figs. 12.2a and 12.3b, regulation of the blood flow to the individual nephron involves several oscillatory modes. The two dominating time scales are associated with the period Tsiow 30—40 s of the slow TGF-mediated oscillations and the somewhat shorter time scale Tjast 5—10 s defined by the myogenic oscillations of the afferent arteriolar diameter. The two modes interact because they both involve activation of smooth muscle cells in the arteriolar wall. Our model describes these mechanisms and the coupling between the two modes, and it also reproduces the observed multi-mode dynamics. We can, therefore, use the model to examine some of the phenomena that can be expected to arise from the interaction between the two modes. 

Figure 1. Pathological aspect of Chinese herb nephropathy. Paucicellular interstitial fibrosis around atrophic tubules ( ). Fibrous thickening of the arteriolar walls (arrow). No glomerular lesion. H E staining, original magnification 300x. By courtesy of Dr. M. Depierreux.

Intrinsic defects in these renal adaptive mechanisms could lead to plasma volume expansion and increased blood flow to peripheral tissues, even when BP is normal. Local tissue autoregulatory processes that vasoconstrict then would be activated to offset the increased blood flow. This effect would result in increased peripheral vascular resistance and, if sustained, also would result in thickening of the arteriolar walls. This pathophysiologic component is plausible because increased total peripheral vascular resistance is a common underlying finding in patients with essential hypertension. 

Thiazide diuretics have additional actions that may further explain their antihypertensive effects. Thiazides mobilize sodium and water from arteriolar walls. This effect would lessen the amount of physical encroachment on the lumen of the vessel created by excessive accumulation of intracellular fluid. As the diameter of the lumen relaxes and increases, there is less resistance to the flow of blood, and peripheral vascular resistance drops further. High dietary sodium intake can blunt this effect, and a low salt intake can enhance this effect. Thiazides also are postulated to cause direct relaxation of... 

Jenkner, 1986). The possible cause of this alteration is the decreased elasticity of arteriolar wall, which is the most sensitive indicator of disease progression. 

Arteriolar resistance changes that take place in order to maintain a constant blood flow are explained by the myogenic mechanism. According to this mechanism, vascular smooth muscle contracts in response to stretch. For example, consider a situation in which blood pressure is increased. The increase in pressure causes an initial increase in blood flow to the tissue. However, the increased blood flow is associated with increased stretch of the vessel wall, which leads to the opening of stretch-activated calcium channels in the vascular smooth muscle. The ensuing increase in intracellular calcium results in vasoconstriction and a decrease in blood flow to the tissue toward normal. 

Figure 15.7 Starling principle a summary of forces determining the bulk flow of fluid across the wall of a capillary. Hydrostatic forces include capillary pressure (Pc) and interstitial fluid pressure (PJ. Capillary pressure pushes fluid out of the capillary. Interstitial fluid pressure is negative and acts as a suction pulling fluid out of the capillary. Osmotic forces include plasma colloid osmotic pressure (np) and interstitial fluid colloid osmotic pressure (n,). These forces are caused by proteins that pull fluid toward them. The sum of these four forces results in net filtration of fluid at the arteriolar end of the capillary (where Pc is high) and net reabsorption of fluid at the venular end of the capillary (where Pc is low).

The action of nitrates appears to be mediated indirectly through reduction of MVo2 secondary to venodilation and arterial-arteriolar dilation, leading to a reduction in wall stress from reduced ventricular volume and pressure. Direct actions on the coronary circulation include dilation of large and small intramural coronary arteries, collateral dilation, coronary artery stenosis dilation, abolition of normal tone in narrowed vessels, and relief of spasm. 

At higher concentrations, nitroglycerin also relaxes arteriolar smooth muscle, which leads to a decrease in both peripheral vascular resistance and aortic impedance to left ventricular ejection (decreased afterload). The decreased resistance to ventricular ejection may also reduce myocardial wall tension and oxygen requirements. 

Arteriolar and venous tone (smooth muscle tension) both play a role in determining myocardial wall stress (Table 12-1). Arteriolar tone directly controls peripheral vascular resistance and thus arterial blood pressure. In systole, intraventricular pressure must exceed aortic pressure to eject blood arterial blood pressure thus determines the systolic wall stress in an important way. Venous tone determines the capacity of the venous circulation and controls the amount of blood sequestered in the venous system versus the amount returned to the heart. Venous tone thereby determines the diastolic wall stress. 

Peniciiiamine Taic and other siiicates Tetradecyisuifate Na Vascular lesion in connective tissue matrix of arterial wall, glomerular immune complex deposits, inhibits synthesis of vascular connective tissue Pulmonary arteriolar thrombosis, emboli Sclerosis of veins Glomerulonephritis... 

The factors involved in regulation of GFR are listed in Table 45-3. Autoregulation of renal blood flow and GFR is widely thought to be explained by the myogenic theory. This theory is based on the principle that an increase in the wall tension of the afferent arterioles, brought about by an increase in perfusion pressure, causes automatic contraction of the arteriolar smooth muscle, thus increasing resistance and beeping the flow constant despite the increase in perfusion pressure. 

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