Peripheral resistance units

PCI ADO, pmol/ml CVR, peripheral resistance units/lOOg O2 EXT, ml/dl CSO9, ml/dl... 

The arterial blood pressure (ABP) depends on (1) the volume of blood per unit of time that is forced by the heart into the high-pressure system-cardiac output corresponding to the product of stroke volume and heart rate (beats/ min), stroke volume being determined inter alia by venous filling pressure (2) the counterforce opposing the flow of blood, i.e., peripheral resistance, which is a function of arteriolar caliber. 

Phentolamine is a potent competitive antagonist at both K and k2 receptors (Table 10-1). Phentolamine reduces peripheral resistance through blockade of K receptors and possibly k2 receptors on vascular smooth muscle. Its cardiac stimulation is due to antagonism of presynaptic k2 receptors (leading to enhanced release of norepinephrine from sympathetic nerves) and sympathetic activation from baroreflex mechanisms. Phentolamine also has minor inhibitory effects at serotonin receptors and agonist effects at muscarinic and Hi and H2 histamine receptors. Phentolamine s principal adverse effects are related to cardiac stimulation, which may cause severe tachycardia, arrhythmias, and myocardial ischemia. Phentolamine has been used in the treatment of pheochromocytoma. Unfortunately oral and intravenous formulations of phentolamine are no longer consistently available in the United States. 

Fig. 22.1 Cardiovascular effects of noradrenaline (norepinephrine), adrenaline (epinephrine) and isoprenaline (isoproterenol) pulse rate/min, blood pressure in mmHg (dotted line is mean pressure), peripheral resistance in arbitrary units.The differences are due to the differential a and p agonist selectivities of these agents (see text). (By permission,after GinsburgJ,Cobbold A F I960 ln Vane J R et al (eds) Adrenergic mechanism. Churchill, London)...

Hypertension is defined as a sustained diastolic blood pressure greater than 90 mm Hg accompanied by an elevated systolic blood pressure (>140 mm Hg). Hypertension results from increased peripheral vascular smooth muscle tone, which leads to increased arteriolar resistance and reduced capacitance of the venous system. Elevated blood pressure is an extremely common disorder, affecting approximately 15% of the population of the United States (60 million people). Although many of these individuals have no symptoms, chronic hypertension—either systolic or diastolic—can lead to congestive heart failure, myocardial infarction, renal damage, and cerebrovascular accidents. The incidence of morbidity and mortality significantly decreases when hypertension is diagnosed early and is properly treated. 

In the United States in 1960, Richardson-Merrell sought marketing approval for thalidomide under the brand name Kevadon. It never reached the market because of the resistance of an FDA medical reviewer. Dr. Francis Kelsey. It is said that she was influenced by her previous experience with the antimalarial drug quinidine, which had teratogenic activity. Her misgivings were based on concerns that peripheral neuritis had been observed in adults. This mixture of concern about safety and previous experience combined to overrule the considerable body of preclinical evidence that the drug was safe. Kelsey... 

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