Functional endothelin receptors are present on nuclei in cardiac ventricular myocytes.

This chapter will address the changes which occur in the arterial baroreflex arc in humans with hypertension and in animal models of hypertension. It will touch only briefly on baroreceptor denervation, which has been covered in an earlier chapter.

Baroreceptors and Hypertension

The vascular actions of endothelin-1 (ET-1) reflect the combination of vasoconstrictor ETA and ETB receptors on smooth muscle cells and vasodilator ETB receptors on endothelial cells. The present s...

https://www.physiology.org/doi/pdf/10.1152/ajprenal.00368.2003

Dual constrictor and dilator actions of ETB receptors in the rat renal microcirculation: interactions with ETA receptors

Clinical trials with endothelin receptor antagonists: what went wrong and where can we improve?

Endothelin is a potent vasoconstrictor with a wide range of effects on the heart. Changes in myocardial and circulating levels of endothelin have been described in various experimental models of myocardial ischemia, and in humans with acute myocardial infarction and different forms of angina pectoris. The role played by endothelin in the different states of myocardial ischemia is unclear. However, myocardial damage has been shown to be reduced in several experimental models of myocardial infarction by administering agents that block the action of endothelin. The aim of this review article is to present the current literature concerning the interaction between endothelin and the various forms of myocardial ischemia, and to explore the significance of such interactions.

Endothelin and myocardial ischemia.

To determine whether endothelin, a highly potent vasoconstrictor peptide, may affect cardiac myocyte contractility directly, we studied the effects of synthetic porcine endothelin-1 in cultured chick embryo ventricular cells. Endothelin-1 had a potent chronotropic effect (EC50 0.17 nmol/l) in spontaneously beating cells. The increase in the beating rate was accompanied by a frequency-dependent decrease in the amplitude of contraction. In electrically driven cells (1 Hz), endothelin-1 increased the amplitude of contraction dose-dependently, with an EC50 of 0.3 nmol/l, smaller than that of the calcium channel blocker BAY K 8644 (EC50 3.3 nmol/l), and with an efficacy close to that of BAY K 8644 and isoproterenol. Nicardipine (100 nmol/l) shifted to the right, by two orders of magnitude, the dose-response curve of endothelin-1 for inotropism. These results indicate that endothelin-1 is one of the most potent inotropic agents in cultured cardiac myocytes, and suggest that this effect involves, at least in part, a calcium ion influx through voltage-sensitive calcium channels.

Endothelin has potent direct inotropic and chronotropic effects in cultured heart cells.

The effects of two dihydropyridine derivatives, the calcium channel agonist BAY k 8644 or the antagonist PN 200-110, on the central nervous components of the baroreceptor reflex control of heart rate during activation of baroreceptors by phenylephrine (2 micrograms i.v.) were studied in pentobarbital-anesthetized normotensive (Wistar) rats and spontaneously hypertensive rats (SHR). To rule out an effect on peripheral vessels or on the sinoauricular node (or on both), BAY k 8644 and PN 200-110 were administered intracerebroventricularly (i.c.v.) at doses that did not change blood pressure. Baroreceptor reflex sensitivity was calculated as the slope of the relationship between systolic arterial pressure and heart period. Baroreceptor reflex sensitivity increased with time following the onset of anesthesia. In SHR, injection of BAY k 8644 (3 micrograms/kg i.c.v.) suppressed the time-dependent increase in baroreceptor reflex sensitivity. The inhibitory effect of BAY k 8644 (3 micrograms/kg i.c.v.) on the time-dependent increase in baroreceptor reflex sensitivity was suppressed by pretreatment with PN 200-110 (0.6 microgram/kg i.c.v.) but not with the solvent, indicating that the central effect of BAY k 8644 occurred at the level of specific dihydropyridine binding sites. In addition, the inhibitory effect of BAY k 8644 (3 micrograms/kg i.c.v.) on the time-dependent increase in baroreceptor reflex sensitivity was suppressed by pretreatment with the muscarinic antagonist atropine methylnitrate (80 micrograms/kg i.c.v.) but not with the solvent. In normotensive rats, the time-dependent increase in baroreceptor reflex sensitivity was not significantly altered by BAY k 8644 (3 micrograms/kg i.c.v.).(ABSTRACT TRUNCATED AT 250 WORDS)

Anne Marie Brisac

Papers

Endothelin has potent direct inotropic and chronotropic effects in cultured heart cells.

Central modulation of baroreceptor reflex response to phenylephrine by dihydropyridines in rats.

Central and peripheral cardiovascular effects of the enantiomers of the calcium antagonist PN 200-110.