Blood flow total peripheral resistance

P-Adrenoceptor Blockers. There is no satisfactory mechanism to explain the antihypertensive activity of P-adrenoceptor blockers (see Table 1) in humans particularly after chronic treatment (228,231—233). Reductions in heart rate correlate well with decreases in blood pressure and this may be an important mechanism. Other proposed mechanisms include reduction in PRA, reduction in cardiac output, and a central action. However, pindolol produces an antihypertensive effect without lowering PRA. In long-term treatment, the cardiac output is restored despite the decrease in arterial blood pressure and total peripheral resistance. Atenolol (Table 1), which does not penetrate into the brain is an efficacious antihypertensive agent. In short-term treatment, the blood flow to most organs (except the brain) is reduced and the total peripheral resistance may increase. 

Methyldopa. Methyldopa reduces arterial blood pressure by decreasing adrenergic outflow and decreasing total peripheral resistance and heart rate having no change in cardiac output. Blood flow to the kidneys is not changed and that to the heart is increased. It causes regression of myocardial hypertrophy. 

Total peripheral resistance (TPR) is the resistance to blood flow offered by all systemic vessels taken together, especially by the arterioles, which are the primary resistance vessels. Therefore, MAP is regulated by cardiac activity and vascular smooth muscle tone. Any change in CO or TPR causes a change in MAP. The major factors that affect CO, TPR, and therefore MAP, are summarized in Figure 15.3, as well as in Table 15.1. These factors may be organized into several categories and will be discussed as such ... 

Notes CO cardiac output VR venous return HR heart rate SV stroke volume EDV end-diastolic volume ESV end-systolic volume O blood flow AP pressure gradient R resistance r vessel radius P systolic pressure Piiastoik- diastolic pressure MAP mean arterial pressure TPR total peripheral resistance, P venous pressure Era- right atrial pressure Rv venous resistance. 

Loss of plasma volume leads to a decrease in MAP. Baroreceptors located in the aortic and carotid sinuses detect this fall in MAP and elicit reflex responses that include an increase in the overall activity of the sympathetic nervous system. Sympathetic stimulation of the heart and blood vessels leads to an increase in cardiac output (CO) and increased total peripheral resistance (TPR). These adjustments, which increase MAP, are responsible for the short-term regulation of blood pressure. Although increases in CO and TPR are effective in temporary maintenance of MAP and blood flow to the vital organs, these activities cannot persist indefinitely. Ultimately, plasma volume must be returned to normal (see Table 19.1). 

Consequently, total peripheral resistance may actually fall, explaining the fall in diastolic pressure that is sometimes seen with epinephrine injection (Figure 9-6 Table 9-4). Activation of these B2 receptors in skeletal muscle contributes to increased blood flow during exercise. Under physiologic conditions, ephinephrine functions largely as a hormone after release from the adrenal medulla into the blood, it acts on distant cells. 

This a2-agonist is converted to methylnorepinephrine centrally to diminish the adrenergic outflow from the CNS, leading to reduced total peripheral resistance and a decreased blood pressure. Cardiac output is not decreased and blood flow to vital organs is not diminished. Because blood flow to the kidney is not diminished by its use, a-methyldopa [meth ill DOE pa] is especially valuable in treating hypertensive patients with renal insufficiency. The most common side effects of a-methyldopa are sedation and drowsiness. 

Arterial BP is generated hemodynamically by the interplay between blood flow and the resistance to blood flow. It is defined mathematically as the product of cardiac output (CO) and total peripheral resistance (TPR) according to the following equation ... 

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. 

Blood flow to skeletal muscles is increased by therapeutic doses, due in part to powerful /32-mediated vasodilation that is only partially counterbalanced by vasoconstrictor via the a receptors that also are present. If an a receptor antagonist is given, vasodilation in muscle is more pronounced, total peripheral resistance is decreased, and mean blood pressure falls Epi reversal). After the administration of a nonselective p receptor antagonist, Epi produces only vasoconstriction and a considerable pressor effect. 

The long-term fall in systemic blood pressure observed in hypertensive individuals treated with ACE inhibitors is accompanied by a leftward shift in the renal pressure-natriuresis curve (Figure 30-5) and a reduction in total peripheral resistance that varies in different vascular beds. Vasodilation in the kidney is a relatively constant finding that is explained by the exquisite sensitivity of renal vessels to the vasoconstrictor actions of Angll. Increased renal blood flow occurs without an increase in GFR thus, the filtration fraction is reduced. Both the afferent and efferent arterioles are dilated. Blood flows in the cerebral and coronary beds, where autoregulatory mechanisms are powerful, generally are well maintained. 

Because of the potential for ANF to be involved in blood pressure control, several investigators have studied its effects on the cardiovascular system of normal and hypertensive animals. In anesthetized normotensive and spontaneously hypertensive rats, atrial extract decreased arterial blood pressure in association with a decrease in both total peripheral resistance and cardiac contractility.il Also, a negative chronotropic effect has been reported in rats.H Dahl salt-sensitive rats appear to have greater amounts of ANF in their atria, but are hyporesponsive when exogenous material is injected.90 Results from this study also suggest an increase in renal papillary plasma flow and a washout of the medullary osmotic gradient, factors which could contribute significantly to the associated natriuresis and diuresis. Increased medullary and inner cortical blood flow also were reported in normotensive rats.118... 

Cardiac output is closely related to metabolic rate, since the heart supplies oxygen and nutrients for metabolism. Table 17.2 gives a comparison of cardiac output in several species. Deviations from this equation have been found in very small mammals [White et al., 1968]. Since blood pressure is invariant, cardiac output is limited by the total peripheral resistance to blood flow of the mammalian systemic arterial tree, which is obtained as... 

Quinterenol (XIII) was found to have g-adrenergic stimulant properties. Thus the drug increased hind limb blood flow and lowered total peripheral resistance in the dog to the same extent as did papaverine but had a considerably longer duration of action. All cardiovascular effects of quinterenol were blocked by the 8-receptor blocking agent, propranalol. 

It causes coronary vasodilatation and increases coronary blood flow. It reduces the total peripheral vascular resistance and systolic and diastolic blood pressure is reduced. It causes reflex tachycardia. 

The prevention and treatment of severe metabolic acidosis in patients with kidney disease is also important to prevent the development of renal bone disease, fatigue, decreased exercise tolerance, reduced cardiac contractility, and increased ventricular irritability. Metabolic acidosis also appears to stimulate protein catabolism, which can contribute to a negative nitrogen balance and lower albumin concentrations, as well as cause growth retardation in children. Lower serum bicarbonate levels in peritoneal dialysis patients have also been associated with a higher hospitalization rate and longer hospital stays. Severe acidemia (blood pH <7.1 to 7.2) suppresses myocardial contractility, predisposes patients to cardiac arrhythmias, and may lead to a decrease in total peripheral vascular resistance and blood pressure, reduced hepatic blood flow, and impaired oxygen delivery. ... 

Propofol Propofol produces anesthesia at a rate similar to that of the intravenous barbiturates, and recovery is more rapid. Propofol has antiemetic actions, and recovery is not delayed after prolonged infusion. The drug is commonly used as a component of balanced anesthesia and as an anesthetic in outpatient surgery. Propofol may cause marked hypotension during induction of anesthesia, primarily through decreased peripheral resistance. Total body clearance of propofol is greater than hepatic blood flow, suggesting that its elimination includes other mechanisms in addition to metabolism by liver enzymes. 

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