Peripheral arteriolar constriction

With advancing age, the patient with essential hypertension progressively changes his hemodynamic pattern into one of normal cardiac output with increased peripheral arteriolar constriction and, finally, later in the natural course of the disease into one of lower cardiac output and further increase in peripheral vascular resistance ). 

Merely because a substance depresses blood pressure does not make it a true antihypertensive substance. The level of blood pressure is the resultant of several factors the viscosity of the blood, the cardiac output, the volume of circulating blood, and the state of the arterial and arteriolar bed, which determines the peripheral resistance to blood flow, other factors being equal. This discussion has indicated that peripheral resistance through arteriolar constriction may be affected by renal blood flow and the production of circulating pressor agents. Therefore, a definition of a true antihypertensive substance is necessary, in order that we be not misled by depressor substances which lower blood pressure at a detriment to the body s economy. 

Midodrine is a prodrug, whose active metabolite is relatively selective for vascular postjunctional alphai-adrenoceptors and therefore increases peripheral resistance by arteriolar constriction, with some veno-constriction in capacitance vessels (1). It has minimal activity in the central nervous system, since it does not cross the blood-brain barrier. It can be given orally and has a systemic availabihty of over 90% by this route. The half-life of the active deglycinated metabolite is relatively short (2-3 hours). The dosage range is 2.5-10 mg tds, and is usually toward the upper end of this range. 

Contraction of veins forces reserved blood into circulation, which increases diastolic pressure, while the increased circulating blood volume, coupled with arteriolar constriction (which increases the total peripheral resistance), increases systolic pressure. The drug simultaneously causes norepinephrine to be released from sympathetic nerve terminals, which increases cardiac output and antagonizes the effects of vagal compensation. 

Acute changes in cardiac contractility, peripheral resistance, or blood volume may transiently exert differential effects on cardiac output and venous return. Except for such brief disparities, however, such factors simply alter flow around the entire circuit. It is irrelevant whether one thinks of that flow as cardiac output or venous return. All too frequently authors have ascribed the reduction in cardiac output during hemorrhage, for example, to a decrease in venous return. Such an explanation, of course, is a blatant example of circular reasoning, in its most literal sense. Hemorrhage reduces blood flow around the entire circuit, mainly because the diminished blood volume and generalized arteriolar constriction lead to a reduction in the cardiac preload. To attribute the reduction in cardiac output to a curtailment of venous return is equivalent to ascribing the decrease in systemic blood flow to a decrease in systemic blood flow ... 

Smooth muscles and vascular smooth muscles Prostaglandins E2 and I2 cause arteriolar dilation in the systemic and pulmonary vascular beds. Prostaglandins and E2, as well as thromboxane B2, constrict the human umbilical cord. Leukotrienes C4 and D4, which release prostaglandin E, decrease peripheral vascular resistance. 

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