Upregulation of the Vascular Alpha-1 Receptor in Malignant Doca-salt Hypertension

In this investigation we describe regulation of the vascular alpha-1 receptor and functional properties of resistance vessels in malignant hypertensive DOCA-salt rats (DOCA-salt). Uninephrectomized control and DOCA-salt rats were maintained for 6 weeks; microscopic renal morphology provided an index of vascular injury. Radioligand binding studies indicated a striking increase in the density of mesenteric alpha-1 binding sites in DOCA-salt (542 +/- 44 fm/mg) vs. salt control (206 +/- 4 fm/mg) and water control (223 +31 fm/mg) P less than .01. The affinity of the receptor for the radioligand [125I] (+/-) BE 2254 was reduced in DOCA-salt rats. Electrical nerve stimulation and agonist dose response curves were performed on isolated perfused mesenteric arteries. A singular correlation between increased receptor density and vascular responses in DOCA-salt rats could not be demonstrated. The norepinephrine (NE) content of mesenteric arteries was reduced in DOCA-salt (1001 +/- 32 ng/g) vs. water control (1522 +/- 44 ng/g) and saline control (1538 +/- 30 ng/g) P less than .01. Our results indicate, upregulation of the mesenteric alpha-1 receptor occurs in DOCA-salt rats, however, additional factors participate in the vascular response to adrenergic stimulation in this model.