Vascular reactivity to vasopressin during diabetes: gender and regional differences Angel Luis Garcı ´a-Villalo ´n * , Elena Sanz, Luis Monge, Nuria Ferna ´ndez, Marı ´a Angeles Martı ´nez, Bele ´n Climent, Godofredo Die ´guez Departamento de Fisiologı ´a, Facultad de Medicina, Universidad Auto ´noma, Arzobispo Morcillo 2, 28029 Madrid, Spain Received 13 June 2002; received in revised form 19 November 2002; accepted 22 November 2002 Abstract The isometric response to vasopressin of 2-mm-long segments of basilar, coronary, renal and tail arteries from male and female, control (normoglycemic) and streptozotocin-induced diabetic rats was studied. Vasopressin (10 À12 –3Â10 À8 M) produced arterial concentration- dependent contraction, with a lower potency in coronary arteries from female than from male rats, and was similar for both genders in basilar, renal and tail arteries. This contraction was reduced by diabetes in basilar and coronary arteries, increased in renal arteries, and not modified in tail arteries, in both genders. Inhibition of nitric oxide synthesis with N W -nitro-L-arginine methyl ester (L-NAME, 10 À4 M) increased the contraction to vasopressin in coronary arteries from control female and diabetic female rats; as well as in renal arteries from control male and control female rats, but not in any other experimental group. Inhibition of cyclooxygenase with meclofenamate (10 À5 M) reduced the contraction to vasopressin in basilar arteries from diabetic female rats and in renal arteries from diabetic male rats, but not in any other experimental group. These results suggest that the response to vasopressin (a) has lower potency in female coronary arteries due to higher nitric oxide production; (b) is reduced by diabetes in basilar and coronary arteries from both genders, by mechanisms independent of nitric oxide and prostanoids; and (c) is increased by diabetes in renal arteries due to reduced production of nitric oxide in females, and to both reduced production of nitric oxide and increased production of prostanoids in males. Therefore, the effects of diabetes on vascular reactivity to vasopressin may differ between vascular beds, and the mechanisms underlay these effects may be distinct between genders. D 2002 Elsevier Science B.V. All rights reserved. Keywords: Cerebral artery; Coronary artery; Renal artery; Tail artery; Nitric oxide (NO); Prostanoid 1. Introduction Cardiovascular abnormalities are some of the most serious complications of diabetes mellitus (Nathan, 1993). For this reason, the vascular reactivity to vasoactive agents during this disease has been the subject of intensive investigation (Tom- linson et al., 1992). One aspect of this subject is the study of diabetic vascular alterations in males and females. It is known that cardiovascular diseases in the general, non-diabetic population are more frequent in men than in premenopausal women (Douglas, 1997; Hayward et al., 2000), and this has been related to the protective effects of ovarian hormones (Mendelsohn and Karas, 1999). However, diabetes may produce a relatively greater impairment in the female cardi- ovascular system, so the difference between men and women regarding cardiovascular diseases disappears in the diabetic patients (Farmer and Gotto, 1997). In agreement with this notion, it has been found that diabetes reduces in females but not in males the relaxation to acetylcholine of rat basilar artery (Mayhan et al., 2002) and rat aorta (Pinna et al., 2001), and the relaxation of human leg circulation to metacholine (Steinberg et al., 2000). However, for other vascular stimuli diabetes may produce a greater affectation of blood vessels from males, as diabetes reduces the vasodilatation to a nitric oxide donor in iliac arteries of male but not of female rats (Martı ´nez-Nieves and Dunbar, 1999), and diabetes increases the contraction to prostanoids in the pulmonary circulation of male but not of female rats (Russ and Tobin, 1998). Knowledge of vascular reactivity to vasopressin during diabetes could be of interest as this peptide may be of relevance for diabetic cardiovascular pathophysiology. Osmoregulation is disturbed during diabetes, and it has been reported that the plasmatic levels of vasopressin are 0014-2999/02/$ - see front matter D 2002 Elsevier Science B.V. All rights reserved. doi:10.1016/S0014-2999(02)02826-1 * Corresponding author. Tel.: +34-1-3975412; fax: +34-1-3975324. E-mail address: angeluis.villalon@uam.es (A.L. Garcı ´a-Villalo ´n). www.elsevier.com/locate/ejphar European Journal of Pharmacology 459 (2003) 247 – 254