Presynaptic alpha- and beta-adrenoceptor stimulation and norepinephrine release in the spontaneously hypertensive rat.

Abstract

A study was designed to measure norepinephrine [NE] release during sympathetic nerve stimulation and evaluate the presynaptic inhibitory and facilitatory actions of .alpha.-adrenoceptor and .beta.-adrenoceptor agonists, respectively, in the isolated perfused kidney of normotensive Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR). Periarterial nerve stimulation (0.25-32 Hz) caused a significantly greater release of NE, which was measured as total tritium overflow, in the SHR. The vasoconstrictor responses to periarterial nerve stimulation as well as to NE, angiotensin II and BaCl were also significantly greater in the SHR. Presynaptic actions of tramazoline, an .alpha.2-adrenoceptor agonist, and salbutamol, a .beta.2-adrenoceptor agonist, on NE release were determined during periarterial nerve stimulation at 2 Hz. Tramazoline (2 .times. 10-9 to 2 .times. 10-7 M) caused a concentration-dependent inhibition of stimulus-induced release of NE in SHR but not in WKY. While the highest concentration of tramazoline (2 .times. 10-7 M) exerted an inhibitory action in the WKY, this effect was of lesser magnitude than that seen in SHR. Salbutamol (1010 to 10-6 M) produced an increase in NE release during periarterial nerve stimulation; this action of the .beta.-adrenoceptor agonist was similar in both the WKY and SHR. Apparently, NE release during sympathetic nerve stimulation is significantly greater in the SHR, and this phenomenon may contribute to the maintenance of hypertension. While presynaptic .beta.-adrenoceptor function is similar in both the WKY and SHR, presynaptic .alpha.-adrenoceptors are supersensitive in the SHR. This supersensitivity may be of physiological importance in curtailing an already greater release of NE present in the SHR.