Alpha‐adrenergic blockers: Mechanism of action, blood pressure control, and effects on lipoprotein metabolism

Abstract

Summary: The sympathetic nervous system plays a major role in the pathogenesis of essential hypertension and is mediated by the a and P receptors. The a receptor is divided into two types, aI and a2, based on response to epinephrine and norepinephrine. a ,-Adrenergic receptors have a high affinity for drugs such as pmzosin, doxazosin, and terazosin, which act to reduce blopd pressure by selective blockade of the receptor. These agents provide a rational approach to the treatment of hypertension by correcting elevated total peripheral resistance, the fundamental hemodynamic abnormality in essential hypertension. In contrast, early a-adrenergic receptor blockers nonselectively blocked both a I and a2 receptors and were unsuitable as antihypertensive agents because they induced tachycardia and patients developed a tolerance to them rapidly. a,-Adrenergic blockers also have beneficial effects on plasma lipoproteins, tending to decrease levels of triglycerides and cholesterol and increase levels of highdensity lipoprotein (HDL) cholesterol and the HDL cholesterol/total cholesterol ratio. P-Adrenergic blockers, such as propranolol and atenolol, have been shown to have an adverse effect on the lipid profile by tending to increase levels of triglycerides and decrease HDL cholesterol. A number of mechanisms contribute to these effects, in particular, adrenergic modulation of lipoprotein lipase and the triglyceride secretion rate. Doxazosin has been shown to increase the activity of LDL receptors, which may be partly responsible for its beneficial effect on plasma lipids and lipoproteins. Doxazosin is different from other aIadrenergic inhibitors in that its maximal hypotensive effect occurs within 5 or 6 hours after administration in acute dosing studies, making first-dose postural hypotension unlikely, and its long half-life provides 24-h blood pressure control with once-daily dosing.

Genetic and pharmacological analysis of neurotransmitters controlling egg laying in C. elegans

“…Defecation: (1-)$;;CyMC, (+/-) = ll-30% EMC, (+) = 31-80% EMC, (++) = 81-0 0egl-2(n693) did not lay eggs in well assays (Table 1) but did lay eggs on plates in response to phentolamine. * Hedner and Persson (1988); =Mylecharane (1989); d Ereshefsky et al (1989); c Richardson et al (1985); fHytte1 (1994); g Lewis et al (1980);h Stockbrngger (1989); r Nash (1990);J Evansand O'Shea (1978), Dylund (1992), andHo&& et al (1982); XCurtis et al (1970); I Kinney (1985); m Sunahara et al (1993); " Seeman (1987); " Hamik and Peroutka (1989); p Giannini et al (1984Giannini et al ( -1985 Table 2 caption for description of egg-laying assays. The P val ue represents the significance of the difference from the no drug control.…”

Do alpha blockers cause heart failure and stroke? Observations from ALLHAT

“…In the short-term they seem attractive because not only do they lower blood pressure but they also have mildly beneficial effects on plasma lipid levels and also appear to improve insulin sensitivity. 3 The early alpha blocker, prazocin, was not popular because of a rapid first dose effect sometimes causing postural hypotension. Furthermore, it had to be given three times per day.…”

Role of brainstem thyrotropin-releasing hormone-triggered sympathetic overactivation in cardiovascular mortality in type 2 diabetic Goto–Kakizaki rats

“…25 Peripheral inflammation, oxidative stress, dyslipidemia and altered renin-angiotensin system function have important roles in the pathology of obesity, T2D and hypertension, and are all associated with overactivation of adrenal-sympathetic functions. 3,[42][43][44] These factors may also contribute to the fatal cardiovascular responses to i.c. injection of TRH-analog observed here in GK rats.…”