Norepinephrine effect on in situ venous membrane potential in spontaneously hypertensive rats.

Comparative in situ (innervation and circulation intact) and in vitro measurements of transmembrane potential (Em) were made in vascular smooth muscle cells (VSM) of small (300-500 micrometers) veins of an externalized intestinal mesenteric loop in 13- to 15-wk-old anesthetized spontaneously hypertensive rats (SHR) and Wistar-Kyoto normotensive controls (WKY). During suffusion with physiological salt solution (PSS), the mean in situ Em in SHR was significantly lower (-34 +/- 0.8 mV) than in WKY (-49 +/- 1.3 mV). In situ neural blockade with 1 microgram/ml tetrodotoxin (TTX) in PSS hyperpolarized venous Em in SHR (-45 +/- 1.7 mV) but not in WKY. In vitro Em in SHR (-51 +/- 1.0 mV) and WKY (-54 +/- 1.1 mV), though significantly elevated above respective in situ values, did not differ significantly from each other and were not altered by TTX. Increasing norepinephrine (NE) concentrations in the PSS gradedly depolarized the venous VSM of WKY in situ to a plateau Em of -32 +/- 0.9 mV at 6 microM (1 micrograms/ml) NE but had no significant depolarizing effect on the less-polarized venous VSM of SHR. However, after addition of 1 micrograms/ml TTX to the PSS, the in situ Em in SHR followed a depolarizing NE dose-response curve similar to that observed in WKY (with or without TTX). These results support the hypothesis that the neurogenic vasoconstrictor component of VSM tone is significantly elevated in mesenteric veins of the SHR model of essential hypertension.