SUMMARY1. The tunica media of the proximal segments of the pulmonary vein is made up of cardiac muscle cells. The electrical activity of this cardiac portion of the pulmonary vein was studied with intracellular micro-electrodes in isolated preparations.2. All-or-none action potentials were recorded in all cardiac muscle cells in response to electrical stimulation. These action potentials did not propagate into the adjoining smooth muscle cells.3. There were differences in properties between cells at the distal end of the cardiac pulmonary vein close to the smooth muscle and those close to the heart. In quiescent preparations, cells at the distal end had resting potentials which averaged 66 mV compared with 71 mV at proximal sites. Action potentials were also smaller and shorter in duration in cells at the distal end.4. In spontaneously active preparations, pace-making potentials were observed in cells at the distal end while cells close to the heart showed a stable diastolic potential between action potentials. The spontaneous activity of the pulmonary vein was influenced by both inhibitory and excitatory nerves.5. The interaction between the pulmonary vein and atrial activities was studied in spontaneously active atrial-pulmonary vein preparations. Action potentials recorded from the pulmonary vein always followed those from the right atrium. Electrical stimulation at the pulmonary vein generated action potentials that propagated back into the right atrium.6. This study demonstrated that isolated pulmonary veins were capable of independent pace-making activity. However the activity of the pulmonary vein was dominated by the SA node in atrial-pulmonary vein preparations under normal conditions.

The characteristics of the hyperpolarization response to acetylcholine (ACh) in endothelial cells from the guinea pig coronary artery were studied by microelectrode recording technique. ACh (30 nM to 3 ,uM) induced membrane hyperpolarization in a dose-dependent manner. The sustenance of the response required the presence of external calcium. The hyperpolarization was not affected by nifedipine (1 ,uM) but was inhibited by the potassium channel blockers charybdotoxin (10 nM), tetraethylammonium (1 mM), and 4-aminopyridine (0.5 mM).Glibenclamide (10 ,M) and apamin (1 ,uM) were not effective. The inhibitors of endotheliumderived relaxing factor/nitric oxide synthesis Nw-nitro L-arginine (50 ,M) and NG-monomethyl L-arginine (30 ,uM) had no effect on the resting membrane potential or the ACh-induced responses. No hyperpolarization was observed with application of sodium nitroprusside (10 ixM) or 8-bromo-cGMP (0.1 ,uM). Ouabain (10 tM) depolarized the membrane significantly by 5 mV, but the ACh hyperpolarization was not affected. Indomethacin (10 JAM) was without effect on the resting membrane potential or the hyperpolarization to ACh. These results show that ACh-induced hyperpolarization is dependent on external calcium and can be inhibited by certain potassium channel blockers. The hyperpolarization response is not mediated by endothelium-derived relaxing factor/nitric oxide, cGMP, a cyclooxygenase product, or stimulation of the Na-K pump. (Circulation Research 1992;70:257-263) T he relaxation response to acetylcholine (ACh) in vascular tissues is dependent on the presence of an endothelium. In many cases, the relaxation can be attributed to the release of an endothelium-derived relaxing factor (EDRF).' It is now generally acknowledged that nitric oxide (NO) or a nitrosothiol compound is the EDRF and L-arginine is the precursor.2 The heme moiety of soluble guanylate cyclase is the NO receptor, and vasorelaxation is associated with an increase in the cGMP level.2Another endothelium-dependent response to ACh in vascular smooth muscle cells is membrane hyperpolarization.3 The cellular mechanism mediating endothelium-dependent hyperpolarization is distinct from that of EDRF/NO.3 For example, vasorelaxation and production of cGMP induced by EDRF/NO are inhibited by methylene blue and hemoglobin.2 However, the hyperpolarization in re-

SUMMARY Neonatal sympathectomy of spontaneously hypertensive rats (SHR) and control Wistar-Kyoto rats (WKY) was performed by a combined treatment with antiserum to nerve growth factor and guanethidine during the first 4 weeks after birth. The development of hypertension was completely prevented in the treated SHR: at 28 to 30 weeks of age, systolic blood pressure of treated SHR was 139 ± 2 mm Hg as compared with 195 ± 8 mm Hg in untreated SHR. The extent of sympathectomy was verified by histofluorescence. Fluorescence histochemistry for catecholamine-containing nerves showed a complete absence of adrenergic nerves in the mesenteric arteries of treated rats. A supersensitivity to norepinephrine was exhibited by mesenteric arteries, anococcygeus muscle, and tail arteries from the treated SHR and WKY. In the mesenteric vascular bed, maximal response to norepinephrine was significantly reduced by sympathectomy. Sympathectomy also abolished the responses (e.g., generation of excitatory junctional potentials) of tail arteries to electrical stimulation of perivascular nerves. Morphometric measurements of three categories of mesenteric arteries showed that sympathectomy had no effect on the hypertrophic change of smooth muscle cells in the conducting vessels, but it prevented the hyperplastic changes of the muscle cells from reactive, muscular arteries and small resistance vessels. These results suggest that one of the primary roles of the overactive sympathetic nervous system in the development of hypertension in SHR is manifested through its trophic effect on the arteries of SHR. This trophic effect appears to cause a hyperplastic change in the smooth muscle cells in the reactive and resistance vessels, thereby contributing to the development of hypertension in older SHR. (Hypertension 10: 328-338, 1987) KEY WORDS • sympathetic nervous system • hypertension • arteries • spontaneously hypertensive rats • nerve growth factor • guanethidine

1. The response of rat tail arteries to stimulation of perivascular nerves was studied with intracellular micro‐electrodes. 2. E.j.p.s were recorded from all smooth muscle cells. With higher stimulus strength, a slow depolarization that lasted for more than 30 sec also appeared. Repetitive stimulation was more effective in eliciting this slow component than were single pulses. 3. E.j.p.s were resistant to phentolamine and yohimbine. However, guanethidine and sympathetic denervation with reserpine and 6‐hydroxydopamine depressed e.j.p.s. 4. The slow depolarization was readily blocked by phentolamine (1 x 10(‐6) g/ml.) and potentiated by cocaine (1 x 10(‐6) g/ml.). 5. It is proposed that vascular smooth muscle activity can be regulated neurally by both the e.j.p. and the slow depolarization.

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