James D. Banting

Acute hypertension after nitric oxide synthase inhibition is mediated primarily by increased endothelin vasoconstriction

Objective To determine the quantitative roles played by the different vasoconstrictor systems in the acute pressor response in conscious rats before and after inhibition of nitric oxide synthase with Nw-nitro-L-arginine methyl ester (L-NAME). Methods In conscious male Sprague-Dawley rats, previously instrumented with aortic and venous catheters, the contributions of the different systems were assessed by maximal cumulative pharmacological blockade of α1-adrenoceptors (1 mg/kg prazosin intraperitoneally), AT1 receptors (30 mg/kg losartan intraperitoneally) and V1/V2 receptors (10 mg/kg [(β-mercapto-β,β-cyclopenta-methyl-enepropionyl1, O-Et-Tyr2-Val4-Arg8]-vasopressin per min intravenously). In addition, the contribution of endothelin-1-induced vasoconstriction in response to 100 mg/kg L-NAME intraperitoneally to the hypertension was assessed by administering 5–100 mg/kg ETA/ETB receptor antagonist PD145 065 intravenously under three different conditions: as the last step of a series of antagonists in the cumulative pharmacological blockade after having induced the L-NAME pressor response; alone before L-NAME treatment; and alone after the full development of the L-NAME pressor response. A separate group of rats was treated acutely with 30 mg/kg losartan intraperitoneally or pretreated for 3 days with 30 mg/kg angiotensin I converting enzyme inhibitor enalapril via drinking water alone or in combination with 1 % salt was used to assess the role of the renin-angiotensin system in the L-NAME-induced hypertension. Results Short-term administration of the combined ETA/ETB receptor antagonist PD 145 065 did not change the arterial pressure under control conditions. Inhibition of the reninangiotensin system, α1-adrenoceptors or vasopressin receptors alone or in combination did not alter the magnitude of the L-NAME pressor response. In contrast, our results show that both treatments before and during acute nitric oxide synthase blockade hypertension using the ETA/ETB receptor antagonist PD 145 065 abolished almost completely (approximately 85%) the pressor response. Conclusions These studies indicate that the predominant mechanism of hypertension, at least in the acute phase, after acute nitric oxide synthase blockade with L-NAME is associated with a marked increase in ETA/ETB receptor activation rather than with increases in α1, AT1 and V1/V2 receptor activation. It remains to be determined whether endothelin participates also in the chronic phase of nitric oxide-deficient hypertension.

Vascular control mechanisms in penile erection: phylogeny and the inevitability of multiple and overlapping systems

A co-ordinated series of vascular events underlie the generation of a penile erection. The control and regulation of this simple event is, in fact, a complex of interactions occurring at multiple levels. Many of these individual pathways and responses have been studied extensively. The understanding of the necessity for the integration between the individual pathways into a complex of series and parallel coupled mechanisms provides a rationale for the development of a framework of multiple and overlapping systems. This paper sets out some of the principles of integrated and balanced control of vasodilation and vasoconstriction in the penis. In addition, the role of growth induction and regression and the importance of time as a factor in studying penile structure and function is discussed.