Arteriolar response

Depletion of body sodium. This reduces plasma volume (transiently), and reduces arteriolar response to noradrenaline (norepinephrine)... 

Imlg JD, Deichmann PC Afferent arteriolar responses to ANG II involve activation of PLA2and modulation by lipoxygenase and P-450 pathways. Am.J.Physiol 273 F274-F282,1997... 

Carmines PK, Navar EG Disparate effects of Ca channel blockade on afferent and efferent arteriolar responses to angiotensin II. Am J Physiol 256 1015-1020,1989... 

Ichihara A, Imig JD, Navar LG Cyclooxygenase-2 modulates afferent arteriolar responses to increases in pressure. Elypertension 34 843-847,1999... 

Z. Sui, and R.J. Roman (1994). Cytochrome P-450 inhibitors alter afferent arteriolar responses to elevations in pressure. Am. J. Physiol. 266, H1879-H1885. 

Vasodilators. Hydralazine causes direct relaxation of arteriolar smooth muscle. An important consequence of this vasodilation, however, is reflex tachycardia (T CO). It may also cause sodium retention (T plasma volume). The resulting increase in CO tends to offset effects of the vasodilator. Therefore, these drugs are most effective when administered along with sympathetic agents such as P-adrenergic receptor antagonists, which prevent unwanted compensatory responses by the heart. 

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. 

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. 

Atherosclerotic lesions occluding Rj increase arteriolar resistance, and R2 can vasodilate to maintain coronary blood flow. With greater degrees of obstruction, this response is inadequate, and the coronary flow reserve afforded by R2 vasodilation is insufficient to meet oxygen demand. Relatively severe stenosis (greater than 70%) may provoke ischemia and symptoms at rest, whereas less severe stenosis may allow a reserve of coronary blood flow for exertion. 

Ang II is a very potent pressor agent—on a molar basis, approximately 40 times more potent than norepinephrine. The pressor response to intravenous Ang II is rapid in onset (10-15 seconds) and sustained during long-term infusions. A large component of the pressor response is due to direct contraction of vascular—especially arteriolar—smooth muscle. In addition, however, Ang II can also increase... 

Further in vivo studies revealed that the arteriolar constriction that follows mast cell activation via inosine, is the result of histamine and thromboxane release and that A3AR is involved in mediating this response (Shepherd and Duling 1996 Shepherd et al. 1996 Fozard et al. 1996 Reeves et al. 1997). Inosine, which does not bind to Aj or A2 receptors, thus elicits a monophasic arteriolar constrictor response distinct from the multiphasic dilator/constrictor response to adenosine (Jin et al. 1997). 

Figure 1 shows the effect of traumatic or unpleasant interview on blood pressure, cardiac stroke volume, renal blood flow, and the fraction of the renal blood flow that was filtered at the glomeruli (filtration fraction). In response to the interview both the systolic and diastolic blood pressure and the stroke volume of the heart increased. There was a decrease in the flow of blood through the kidney, and this decrease was due predominantly to an efferent arteriolar constriction since the filtration fraction was increased somewhat. 

When injected intravenously, kinins produce a rapid fall in blood pressure that is due to their arteriolar vasodilator action. The hypotensive response to bradykinin is of very brief duration. Intravenous infusions of the peptide fail to produce a sustained decrease in blood pressure prolonged hypotension can only be produced by progressively increasing the rate of infusion. The rapid reversibility of the hypotensive response to kinins is due primarily to reflex increases in heart rate, myocardial contractility, and cardiac output. In some species, bradykinin produces a biphasic change in blood pressure—an initial hypotensive response followed by an increase above the preinjection level. The increase in blood pressure may be due to a reflex activation of the sympathetic nervous system, but under some conditions, bradykinin can directly release catecholamines from the adrenal medulla and stimulate sympathetic ganglia. Bradykinin also increases blood pressure when injected into the central nervous system, but the physiologic significance of this effect is not clear, since it is unlikely that kinins cross the blood-brain barrier. 

Our next problem concerns the dynamic response of the arteriolar system to the signal from the mascula densa cells. This response is restricted to that part of the afferent arteriole that is closest to the glomerulus. Hence, the afferent arteriole is divided into two serially coupled sections of which the first (representing a fraction (3 of the total length) is assumed to have a constant flow (or hemodynamic) resistance, while the second (closer to the glomerulus) is capable of varying its diameter and hence the flow resistance in dependence of the tubuloglomerular feedback activation ... 

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] ... 

Fig. 12.5 One-dimensional bifurcation diagram for the single-nephron model obtained by varying the slope a of the open-loop response characteristics, r is the normalized arteriolar radius. The delay in the tubuloglomerular feedback is T = 16 s.

Hydralazine was one of the first orally active antihypertensive drugs marketed in the United States. Its structure is shown in Figure 12.4. Initially, the drug was used infrequently because of its propensity to produce reflex tachycardia and tachyphylaxis. However, with a better understanding of the compensatory cardiovascular responses that accompany use of arteriolar vasodilators (the drug has little or no effect on venous smooth muscle), hydralazine was combined with sympatholytic agents and diuretics with greater therapeutic success. 

These processes are slower than the very swift destruction of acetylcholine at the neuromuscular junction by extracellular acetylcholinesterase seated alongside the receptors. This difference reflects the differing signalling requirements almost instantaneous (millisecond) responses for voluntary muscle movement versus the much more leisurely contraction of arteriolar muscle to control vascular resistance. 

The aim has been to produce peripheral arteriolar vasodilatation without a concurrent significant drop in blood pressure, so that an increased blood flow in the limbs will result. Drugs are naturally more useful in patients in whom the decreased flow of blood is due to spasm of the vessels (Raynaud s phenomenon) than where it is due to organic obstructive changes that may make dilatation in response to drugs impossible (arteriosclerosis, intermittent claudication, Buerger s disease). 

The influence of neuronal nitric oxide synthase (nNOS) on renal arteriolar tone has been studied in the perfused juxtamedullary nephron preparation [126]. Superfusion with a specific nNOS inhibitor decreased afferent and efferent arteriolar diameters, and these decreases in arteriolar diameters were prevented by interruption of distal volume dehvery by papillectomy. When volume delivery to the macula densa segment was increased, afferent arteriolar vasoconstrictor responses to the nNOS inhibitor were enhanced, but this effect was again completely prevented after papillectomy. In contrast, the arteriolar diameter responses to a nonselective NOS inhibitor were only attenuated by papillectomy. Specific nNOS inhibition enhanced the efferent arteriolar vasoconstrictor response to ANG II but did not alter the afferent arteriolar vasoconstrictor responsiveness to ANG II. In contrast, non specific NOS inhibition enhanced both afferent and efferent arteriolar vasoconstrictor responses to ANG It. This study demonstrates that the modulating influence of nNOS on afferent arteriolar tone of juxtamedullary nephrons is dependent on distal tubular fluid flow and that nNOS exerts a differential modulatory action on... 

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