Sensitivity of Caudal Arteries and the Mesenteric Vascular Bed to Norepinephrine in DOCA-Salt Hypertension

This study was undertaken to determine what factors might contribute to arterial supersensitivity to norepinephrine associated with deoxycorticosterone acetate (DOCA)-sait hypertension in the rat. Experimental groups of male rats were uninephrectomized and 1 week later began receiving twice weekly Injections of DOCA (20 mg/kg s.c. in sesame oil) plus 1% NaCl and 0.2% KC1 in their drinking water. For each experimental group, a group of age-matched male rats underwent a sham operation and received injections of sesame oil and the NaCl-KCl drinking water. Perfused caudal arteries from 3- week-hypertensive rats were supersensitive to intraluminal and extraluminal norepinephrine administration. However, this difference hi sensitivity between hypertensive and control caudal arteries was demonstrable at low rates of perfuslon, 0.5 to 1.0 ml/min, but not at rates of 2.0 to 2.6 ml/min. The supersensitivity was not due to differences hi neuronal uptake or to inhibition of extraneuronal uptake by DOCA. The perfused mesenteric vascular bed from 3- or 6-week-hypertensive rats was also supersensitive to intraluminal norepinephrine. However, the demonstration of supersensitivity hi the mesenteric vasculature was independent of perfusion rate (2.3–6.8 ml/min) and perfusion pressure in the range of 30 to 60 mm Hg. There was little or no supersensitivity to transmural nerve stimulation hi either the caudal artery or the mesenteric vasculature, a finding consistent with the observed decrease hi endogenous norepinephrine content. Microelectrodes were used to determine resting membrane potential hi the smooth muscle cells. No differences hi resting membrane potential were detected between caudal or mesenteric arteries from hypertensive compared with control rats 2, 3, or 6 weeks after initiation of the DOCA-salt regimen. It is concluded that 1) the perfusion rate is a critical factor hi designing experiments to test the sensitivity of caudal arteries to drugs, 2) the perfused mesenteric vascular bed is a useful preparation for studying sensitivity of blood vessels hi hypertension, 3) the supersensitivity of blood vessels hi the DOCA-salt model may be of greater importance relative to circulating catecholamines than to sympathetic innervation, and 4) the supersensitivity of blood vessels to norepinephrine in the DOCA-salt model is not due to changes in neuronal uptake, extraneuronal uptake, or membrane potential of the vascular smooth muscle cells.