Gen. Pharmac. Vol. 27, No 8, pp. 1303-1310, 1996 Copyright © 1996 Elsevier Science Inc. Printed in the USA. ELSEVIER ISSN 0306-3623/96 $15.00 + .00 PII 80306-3623(96)00082-1 All rights reserved REVIEW Local Regulation of Oviductal Blood Flow Angeles Garda-Pascual,* Alicia Labad¢a, Domingo Triguero and Gonzalo Costa DEPARTMENT OF PHYSIOLOGY, FACULTYOF VETERINARY SCIENCES, COMPLUTENSE UNIVERSITY, 28040-MADRm, SPAIN [TEL: + 1 3943843; Fax: + 1 3943864] ABSTRACT. 1. Blood flow to the oviduct is implicated in the genesis and maintenance of oviductal fluid, in this way contributing to the creation of an adequate medium for ovum/embryo physiology. Therefore, factors controlling the tone of the vessels supplying the oviduct would be expected to affect its luminal environment. In addition, cyclic changes in oviductal blood flow have been suggested to have mechanical functions in the transport of the ovum/embryo. 2. The vascular supply to the oviduct has a prominent adrenergic vasomotor control. A dense adren- ergic innervation, together with the presence of a predominant population of (xl-adrenoceptors, provides a contractile regulatory mechanism of oviductal blood flow. No evidence is available on the presence of [3-adrenoceptors. The scanty cholinergic innervation of the mammalian oviduct is mainly confined to the vessels, where acetylcholine (ACh) has a vasodilatatory effect by releasing endothelium-derived relaxing factors. 3. The presence of nerves containing neuropeptides has been shown in the oviduct. Specifically, a high density of neuropeptide Y- and vasointestinal peptide-containing nerve fibers has been found in relation to blood vessels, but their role in the neural control of the oviductal blood flow remains to be established. To date, it is not known whether or not oviductal blood vessels receive perivascular ni- trergic nerves. 4. Relaxing and contracting factors derived from endothelium also seem to have a modulatory role on oviductal vascular tone. Neurotransmitters or autacoids, such as ACh and histamine, acting on en- dothelial receptors, release nitric oxide (NO), which relaxes oviductal arteries through guanylyl cyclase activation and accumulation of cyclic GMP. In addition, the release of an endothelium-derived hyper- polarizing factor (EDHF), distinct from NO, by ACh has been shown in oviductal arteries. It acts through the opening of low-conductance Ca2+-activated K ÷ channels leading to hyperpolarization and relaxation. Furthermore, potent and long-lasting contractions induced by the endothelium-derived con- tractile factor, endothelin (ET), points to its role in the long-term regulation of oviductal vascular tone. 5. A particularly high density of 5-hydroxytryptamine (5-HT) and histamine, present in mast cells clustered in the vicinity of blood vessels, has been described in the oviduct. It is known that histamine elicits a relaxation of oviductal arteries that is partially endothelium-dependent and mediated by the ac- tivation of Hi-receptors. The implication of histamine in both the increase in blood flow and edema around ovulation, as well as the existence of a functional antagonism between histamine and 5-HT in the regulation of oviductal blood flow, await further investigation. 6. Other factors, such as relaxing and contracting cyclooxygenase-derivedproducts, may also partici- pate in the modulation of blood flow to the oviduct. 7. An overall endocrine regulation of the oviductal vascular supply exists, acting by both direct ef- fects on smooth muscle and modulation of neural and autocrine factors. This control enables cyclic changes in blood flow to the oviduct that are tightly coupled to the reproductive functions of the tube. Copyright © 1996 Elsevier Science Inc. GEN PHARMAC27;8:1303-1310, 1996. KEY WORDS. Oviduct, vascular, neural control, autocrine regulation INTRODUCTION The oviduct (uterine tube or fallopian tube) provides the necessary environment for gamete survival and maturation, fertilization and early embryo development (Pauerstein and Eddy, 1979; Ellington, 1991). Oviductal secretory and motor activities must be perfectly synchronized to support very distinct processes that develop at dif- ferent tubarian regions in a well defined segmental play: (1) trans- port of spermatozoa to the isthmus where they are stored and capaci- *To whom correspondence should be addressed. Received 3 January 1996; accepted 3 February 1996. tated while they "wait" for ovulation, (2) ovum pickup by the fimbriated portion, followed by its rapid transport to the ampulla at the time of ovulation, where fertilization takes place, and (3), main- tenance of the zygote at the ampullary-isthmic junction for 2-3 days until survival in the uterus is possible. Therefore, it is not surprising that oviductal fluid formation is a very dynamic process to provide, at all these times, the adequate medium for gametes and embryo physiology (Leese, 1988). Oviductal fluid composition has been well characterized in different species as a complex mixture of plasma- derived constituents (selective transudate) plus specific proteins formed by the secretory cells of the oviductal epithelium (Paisley and Mickelsen, 1979; Verhage et al., 1988; Willis et al., 1994). The